<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03237611</url>
  </required_header>
  <id_info>
    <org_study_id>2015-5109</org_study_id>
    <nct_id>NCT03237611</nct_id>
  </id_info>
  <brief_title>Low Dose Aprepitant for Patients Receiving Carboplatin</brief_title>
  <official_title>Phase II Trial Testing the Antiemetic Efficacy of a Single-day Low Dose Aprepitant (or Fosaprepitant) Added to a 5-HT3 Receptor Antagonist Plus Dexamethasone in Patients Receiving Carboplatin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Albert Einstein College of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jacobi Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Albert Einstein College of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates a simple one day prophylaxis of nausea and vomiting for patients who are&#xD;
      getting carboplatin based chemotherapy. In addition to standard oral dexmethasone and oral&#xD;
      ondansetrone, participants will be given a third neurokinin 1 (NK1) antagonist agent, either&#xD;
      Aprepitant or Fosaprepitant (they have been shown to be equally effective) to improve&#xD;
      prevention of nausea and vomiting. No medications need to be taken beyond day 1.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Main predictive factor for the development of CINV is the emetic potential of a given&#xD;
      chemotherapeutic agent. Carboplatin causes both acute and delayed emesis. Guideline groups&#xD;
      have typically classified this agent as moderately emetic (MEC); however, its risk of&#xD;
      inducing vomiting is at the upper range of this classification, and borders on highly emetic.&#xD;
      The recommendation for prevention has been the use of a two-drug regimen (a&#xD;
      5-hydroxytryptamine receptor antagonist (5-HT3RA) plus dexamethasone). The recent randomized&#xD;
      studies have shown that patients given only a 2-drug regimen have about a 50% likelihood of&#xD;
      emesis if they are women, and about a 30% likelihood of emesis if they are men. Major&#xD;
      improvements were reported when a neurokinin-1 receptor antagonist (NK1RA) aprepitant was&#xD;
      added. This improvement is of a similar magnitude to that seen in patients receiving&#xD;
      cisplatin. Similar improvements were also seen in a trial in which the NK1RA antiemetic was&#xD;
      rolapitant rather than aprepitant. The Tanioka and Yahata studies were conducted entirely in&#xD;
      patients with GYN malignancies, and it is not surprising that the control rates are lower in&#xD;
      these all female groups.&#xD;
&#xD;
      The most commonly used NK1RA, aprepitant, is generally given over 3 days. Most studies&#xD;
      indicate that this class of agent gives similar results when given in just one day, or over&#xD;
      multiple days. Recent studies conducted by Roila compared the efficacy of aprepitant on day 1&#xD;
      at a low dose (125 mg) versus the full three day regimen totaling 285 mg in patients&#xD;
      receiving either cisplatin or the combination of anthracyclines plus cyclophosphamide (AC).&#xD;
      In both studies, those patients randomly assigned to just one day of lower dose aprepitant&#xD;
      had control of emesis equal to those receiving multiple days. In both of these trials,&#xD;
      patients assigned to the single day aprepitant arm also received additional antiemetics on&#xD;
      days 2 and 3. However, recent studies have failed to show an advantage for continuing&#xD;
      dexamethasone after day 1 in patients receiving AC (14) or in those receiving cisplatin.&#xD;
      Additionally, a meta-analysis indicated that as long as dexamethasone is given on day 1,&#xD;
      there is no advantage to adding a serotonin antagonist (such as ondansetron) after day 1, and&#xD;
      ondansetron has been shown to be similar to metoclopramide in the delayed emesis phase.&#xD;
      Similarly to studies conducted by Roila, Grunberg and colleagues showed non-inferiority of&#xD;
      single-dose intravenous (IV) fosaprepitant (a phosphorylated analog of aprepitant that is&#xD;
      rapidly converted to aprepitant after IV administration) in a randomized study of patients&#xD;
      receiving cisplatin chemotherapy. Fosaprepitant 115 mg IV has been approved as an alternative&#xD;
      to the 125-mg oral aprepitant dose on day 1 of a 3-day regimen.&#xD;
&#xD;
      There is very little data regarding the efficacy of continued steroids after day 1 in&#xD;
      patients receiving carboplatin. Recent trials fail to show benefit for continuing&#xD;
      dexamethasone after the day of chemotherapy. Aapro and colleagues in a 300 patient trial,&#xD;
      showed that dexamethasone in combination with a 5-HT3RA on day 1 gave similar CINV protection&#xD;
      to a multiple-day dexamethasone. Similarly, a Japanese study showed no difference in&#xD;
      antiemetic efficacy of a single day dexamethasone regimen when prospectively compared with a&#xD;
      3 day dexamethasone regimen; however, the 1 day regimen found significant reductions in&#xD;
      steroid induced side effects. Additionally, a large multinational trial in patients receiving&#xD;
      AC chemotherapy showed that a single dose of dexamethasone on day 1 along with a single day&#xD;
      of NEPA (combination of 5-HT3RA palonosetron with NK1RA netupitant) offers convenient&#xD;
      single-day prophylaxis for both acute and delayed CINV.&#xD;
&#xD;
      Guideline groups are now starting to recommend a 3-agent preventive antiemetic regimen for&#xD;
      patients receiving carboplatin, based on the evidence from the studies discussed above.&#xD;
      However, not all guideline groups have yet made this recommendation. If it can be shown that&#xD;
      a less expensive, more convenient (1-time administration), and potentially safer regimen&#xD;
      performs in the same way for patients receiving carboplatin as it did for those receiving&#xD;
      cisplatin or AC chemotherapy, and similarly to those receiving 3 days of aprepitant with&#xD;
      carboplatin in the recent randomized trials, a new standard may be established.&#xD;
&#xD;
      Objectives. Primary: To determine in patients receiving their first cycle of&#xD;
      carboplatin-based chemotherapy, the complete control rate of emesis (acute and delayed; no&#xD;
      vomiting and no use of rescue medications) with the addition of one dose of the oral&#xD;
      aprepitant or intravenous fosaprepitant to a combination of oral dexamethasone + an oral&#xD;
      5-HT3RA (ondansetron).&#xD;
&#xD;
      Secondary: To estimate the control rate on the second cycle of this chemotherapy in those&#xD;
      patients agreeing to be assessed in the subsequent chemotherapy cycle.&#xD;
&#xD;
      Methods. CINV will be assessed by using the validated MASCC Antisemitism Tool (MAT), which&#xD;
      efficiently evaluates the incidence of vomiting and the severity of nausea and vomiting in&#xD;
      the acute and delayed emesis periods. Patients will be enrolled at Montefiore Medical Center&#xD;
      and at Jacobi Medical Center. Patients will be asked to sign an informed consent form.&#xD;
      Patients will be called on day 2 and 5 to remind about form completion, and will return the&#xD;
      MAT form on their next outpatient visit (or immediately after completion if the patient is an&#xD;
      inpatient). Consent forms then will be kept at a clinical trial center in a file. Case report&#xD;
      forms were developed to capture data relevant to research.&#xD;
&#xD;
      Antiemetic Medication administration. Serious adverse events are not expected since a lower&#xD;
      dose and frequency of FDA approved medications will be given. They may be obtained or&#xD;
      dispensed either by the Jacobi Medical Center, or the Montefiore Medical Center pharmacies,&#xD;
      or aprepitant may be obtained by prescription from an outside pharmacy. If aprepitant is&#xD;
      obtained at an outside pharmacy, the patient will bring the agent to their chemotherapy&#xD;
      appointment; all NK1RA drug administration will be directly observed. The use of either&#xD;
      aprepitant or fosaprepitant will be entirely the choice of the ordering oncologist, as both&#xD;
      agents are equivalent. Ideally all drugs will be given immediately before (within 5 minutes)&#xD;
      chemotherapy; however if a delay occurs up to 2 hours between the antiemetics and&#xD;
      chemotherapy, this will be allowable and no additional dosing will be needed. The time of&#xD;
      administration of the NK1RA in relation to the chemotherapy will be recorded.&#xD;
&#xD;
      All patients will be given 125 mg of aprepitant orally or 115 mg IV of fosaprepitant prior to&#xD;
      the first cycle of carboplatin-based chemotherapy.&#xD;
&#xD;
      Antiemetic drug doses and schedules (same doses in all age and gender groups). Aprepitant or&#xD;
      Fosaprepitant: 125 mg of Aprepitant orally immediately prior to chemotherapy. If&#xD;
      fosaprepitant given instead, it will be administered immediately prior to chemotherapy at&#xD;
      115mg IV (over 20 min). The administration site of the fosaprepitant will be noted and will&#xD;
      be evaluated for possible venous irritation.&#xD;
&#xD;
      Dexamethasone: 20 mg orally immediately prior to chemotherapy. Ondansetron: 16 mg orally,&#xD;
      immediately prior to the chemotherapy.&#xD;
&#xD;
      Patients agreeing to be followed on the second cycle with be assessed in the same way. During&#xD;
      the follow-up visit after the first cycle, patients on study will be asked if they wish to&#xD;
      continue participation during their second chemotherapy cycle (given that they are still&#xD;
      eligible). Patients will not need to sign a separate consent, but will need to give their&#xD;
      verbal affirmation, which will be noted in the case report form. The dosing and timing of the&#xD;
      antiemetics may change according to the results in the first cycle, and other demographic&#xD;
      characteristics, as follows:&#xD;
&#xD;
      Female patients:&#xD;
&#xD;
        -  If there was no vomiting on the first cycle and the antiemetics were well tolerated, all&#xD;
           antiemetics will be given identically to cycle 1.&#xD;
&#xD;
        -  If any vomiting was experienced on the first cycle, patients will instead receive the&#xD;
           typical 3-day aprepitant (125 mg po day 1, and 80 mg po days 2 and 3), or fosaprepitant&#xD;
           150 mg IV (given over 30 minutes) on day 1 only. (The choice of the aprepitant or&#xD;
           fosaprepitant regimen will be at the discretion of the ordering oncologist). Ondansetron&#xD;
           and dexamethasone will be given as on cycle 1. Additionally, 12mg of dexamethasone will&#xD;
           be given on day 3&#xD;
&#xD;
      Male patients:&#xD;
&#xD;
        -  For those aged 50 or older, if there was no vomiting with the first cycle and the&#xD;
           antiemetics were well tolerated, all antiemetics will be given identically to cycle1&#xD;
           except that the aprepitant dose will be reduced to one 80 mg oral administration on day&#xD;
           1. If fosaprepitant is used, it will be given at a total dose of 75 mg over 15 minutes.&#xD;
           All will be given immediately prior to chemotherapy. Ondansetron and dexamethasone will&#xD;
           be given as with cycle1.&#xD;
&#xD;
        -  For those under age 50, if there was no vomiting on the first cycle and the antiemetics&#xD;
           were well tolerated, all antiemetics will be given identically to cycle1.&#xD;
&#xD;
        -  Male patients of any age, if they experienced any vomiting on the first cycle, will&#xD;
           instead receive the typical 3-day aprepitant (125 mg po day 1, and 80 mg po days 2 and&#xD;
           3), or fosaprepitant 150 mg IV (given over 30 minutes) on day 1 only. (The choice of the&#xD;
           aprepitant or fosaprepitant regimen will be at the discretion of the ordering&#xD;
           oncologist). Ondansetron and dexamethasone will be given as on cycle1. Additionally,&#xD;
           12mg of dexamethasone will be given on day 3.&#xD;
&#xD;
      Statistics and Analysis: The investigators will compute the relevant proportions and&#xD;
      corresponding 95% confidence interval. The association of emesis control rate by gender and&#xD;
      other socio-demographic and clinical covariates will be examined using Chi-square test, in&#xD;
      case of small sample size Fisher's exact test will be used. Similar analysis will be&#xD;
      performed to examine the secondary endpoints of complete control, complete emesis control and&#xD;
      complete nausea control in the acute emesis period (first 24 hours after chemotherapy),&#xD;
      delayed emesis period (24 - 120 hour period after chemotherapy) and in the control in the&#xD;
      second cycle of chemotherapy.&#xD;
&#xD;
      Justification of sample size: The investigators anticipate to recruit a total of 50 patients&#xD;
      over one year after protocol approval, from prior experience with usage of carboplatin, the&#xD;
      investigators expect approximately 60% will be females. The investigators project&#xD;
      conservatively a 70% complete control rate based on prior literature (i.e. a 62% complete&#xD;
      control rate in women and an 82% complete control rate in men). To evaluate the adequacy of&#xD;
      the sample size (i.e. number of emesis control observed), precision was computed, as measured&#xD;
      by the width of the 95% CI, with which the proportion of emesis control rate can be&#xD;
      estimated. The width of the 95% CI will be no greater than 26.7% (i.e. +/-the lower and upper&#xD;
      limit of complete control rate will be 55.4% to 82.1%) with the proposed sample size based on&#xD;
      exact Clopper-Pearson formula.&#xD;
&#xD;
      Data and Safety Monitoring Board (DSMB) will be the primary data monitoring and safety group.&#xD;
      Information required in reports by this committee will include 1) summaries of accrual rates&#xD;
      and patterns; 2) information on all adverse events and protocol violations; and 3) efficacy&#xD;
      results at the time of each DSMB meeting, which will not be available to the investigators.&#xD;
      Note, there is no interim analysis specified for this trial. This committee will meet at&#xD;
      least annually. The majority of the members will not be from any of the study institutions,&#xD;
      and no member will be involved in any way with the study. Membership will include as a&#xD;
      minimum: a statistician, a medical oncologist, and a research oncology nurse.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Expired IRB approval on 2/11/21&#xD;
  </why_stopped>
  <start_date type="Actual">October 30, 2018</start_date>
  <completion_date type="Anticipated">August 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Patient scheduled for the first cycle of carboplatin-based chemotherapy will be offered to receive 125mg of oral aprepitant or 115mg of fosaprepitant intravenously for prevention of chemotherapy-induced nausea and vomiting</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete control rate of emesis (this is a composite single endpoint which is commonly used in emesis trials. It encompasses no vomiting and no use of rescue medicines over a total 5-day period)</measure>
    <time_frame>Complete control rate over the 5 day period after chemotherapy</time_frame>
    <description>Treatment efficacy will be determined by measuring complete control rate of emesis based on the visual scale analogue for emesis control, scored by patient from 0 to 10 (MAT form - MASCC Antiemesis Tool)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete control of emesis</measure>
    <time_frame>Complete control rate of emesis will be assessed on day 1 and 5 (both acute and delayed)</time_frame>
    <description>To estimate the control rate on the second cycle of this chemotherapy in those patients agreeing to be assessed in the subsequent chemotherapy cycle.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Chemotherapy-induced Nausea and Vomiting</condition>
  <arm_group>
    <arm_group_label>low dose aprepitant or fosaprepitant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In addition to standard prophylactic antiemetics (Ondansetron 16mg and Dexamethasone 20mg) patients will be given aprepitant 125mg orally or 115mg fosaprepitant intravenously prior to the first cycle of carboplatin-based chemotherapy. No medications will be given afterwards</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aprepitant 125 mg</intervention_name>
    <description>Patient scheduled for the first cycle of carboplatin-based chemotherapy will be offered to receive low doses of aprepitant (125mg of oral aprepitant) or 115mg of fosaprepitant intravenously for prevention of chemotherapy-induced nausea and vomiting</description>
    <arm_group_label>low dose aprepitant or fosaprepitant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fosaprepitant 115 MG</intervention_name>
    <description>Patient scheduled for the first cycle of carboplatin-based chemotherapy will be offered to receive low doses of aprepitant (125mg of oral aprepitant) or 115mg of fosaprepitant intravenously for prevention of chemotherapy-induced nausea and vomiting</description>
    <arm_group_label>low dose aprepitant or fosaprepitant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone will be given as a part of standard CINV prophylaxis for patients receiving carboplatin-based chemotherapy, dosed at 20mg on day 1 of chemotherapy</description>
    <arm_group_label>low dose aprepitant or fosaprepitant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ondansetron 16 MG</intervention_name>
    <description>Ondansetron will be given as a part of standard CINV prophylaxis for patients receiving carboplatin-based chemotherapy, dosed at 16mg on day 1 of chemotherapy</description>
    <arm_group_label>low dose aprepitant or fosaprepitant</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  No prior chemotherapy&#xD;
&#xD;
          -  Confirmed malignancy, scheduled to receive carboplatin monotherapy, or carboplatin in&#xD;
             combination with agents of minimal, low, or moderate emetic potential&#xD;
&#xD;
          -  Laboratory parameters adequate for chemotherapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 3&#xD;
             or 4&#xD;
&#xD;
          -  Presence of nausea and vomiting or use of major antiemetic agents during the 24 hours&#xD;
             before chemotherapy administration&#xD;
&#xD;
          -  Patients receiving radiotherapy within 5 days prior to the carboplatin&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Known allergy to any of the 3 antiemetics&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Gralla, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Albert Einstein College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jacobi Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mascc.org</url>
    <description>MASCC Antiemetic tool (MAT)</description>
  </link>
  <reference>
    <citation>Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med. 2008 Jun 5;358(23):2482-94. doi: 10.1056/NEJMra0706547. No abstract available.</citation>
    <PMID>18525044</PMID>
  </reference>
  <reference>
    <citation>Roila F, Herrstedt J, Aapro M, Gralla RJ, Einhorn LH, Ballatori E, Bria E, Clark-Snow RA, Espersen BT, Feyer P, Grunberg SM, Hesketh PJ, Jordan K, Kris MG, Maranzano E, Molassiotis A, Morrow G, Olver I, Rapoport BL, Rittenberg C, Saito M, Tonato M, Warr D; ESMO/MASCC Guidelines Working Group. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol. 2010 May;21 Suppl 5:v232-43. doi: 10.1093/annonc/mdq194. No abstract available.</citation>
    <PMID>20555089</PMID>
  </reference>
  <reference>
    <citation>NCCN Guidelines, Antiemesis, Version I.2015</citation>
  </reference>
  <reference>
    <citation>Tanioka M, Kitao A, Matsumoto K, Shibata N, Yamaguchi S, Fujiwara K, Minami H, Katakami N, Morita S, Negoro S. A randomised, placebo-controlled, double-blind study of aprepitant in nondrinking women younger than 70 years receiving moderately emetogenic chemotherapy. Br J Cancer. 2013 Aug 20;109(4):859-65. doi: 10.1038/bjc.2013.400. Epub 2013 Jul 16.</citation>
    <PMID>23860530</PMID>
  </reference>
  <reference>
    <citation>Ito Y, Karayama M, Inui N, Kuroishi S, Nakano H, Nakamura Y, Yokomura K, Toyoshima M, Shirai T, Masuda M, Yamada T, Yasuda K, Hayakawa H, Suda T, Chida K. Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy. Lung Cancer. 2014 Jun;84(3):259-64. doi: 10.1016/j.lungcan.2014.03.017. Epub 2014 Mar 27.</citation>
    <PMID>24746177</PMID>
  </reference>
  <reference>
    <citation>Yahata H, et al. Ann Oncol. 25 (Suppl 4): abstract 1481PD, 2014</citation>
  </reference>
  <reference>
    <citation>Gralla R, Jordan K, Rapoport B et al. Assessing the magnitude of antiemetic benefit with the addition of the NK1 receptor antagonist (NK1) aprepitant for all platinum agents: analysis of 1,872 patients (pts) in prospective randomized clinical phase III trials (RCTs) [abstract9057]. J Clin Oncol 2010; 28: 9057.</citation>
  </reference>
  <reference>
    <citation>Hesketh PJ, et al. Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in moderately emetogenic therapy (MEC). J Clin Oncol 33 (Suppl): abstract 9622, 2015</citation>
  </reference>
  <reference>
    <citation>Navari RM, Reinhardt RR, Gralla RJ, Kris MG, Hesketh PJ, Khojasteh A, Kindler H, Grote TH, Pendergrass K, Grunberg SM, Carides AD, Gertz BJ. Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. L-754,030 Antiemetic Trials Group. N Engl J Med. 1999 Jan 21;340(3):190-5. doi: 10.1056/NEJM199901213400304.</citation>
    <PMID>9917226</PMID>
  </reference>
  <reference>
    <citation>Roila F, Ruggeri B, Ballatori E, Fatigoni S, Caserta C, Licitra L, Mirabile A, Ionta MT, Massidda B, Cavanna L, Palladino MA, Tocci A, Fava S, Colantonio I, Angelelli L, Ciuffreda L, Fasola G, Zerilli F. Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study. Ann Oncol. 2015 Jun;26(6):1248-1253. doi: 10.1093/annonc/mdv132. Epub 2015 Mar 5.</citation>
    <PMID>25743855</PMID>
  </reference>
  <reference>
    <citation>Roila F, Ruggeri B, Ballatori E, Del Favero A, Tonato M. Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed emesis in patients with breast cancer: a randomized double-blind study. J Clin Oncol. 2014 Jan 10;32(2):101-6. doi: 10.1200/JCO.2013.51.4547. Epub 2013 Dec 9.</citation>
    <PMID>24323030</PMID>
  </reference>
  <reference>
    <citation>Grunberg S, Chua D, Maru A, Dinis J, DeVandry S, Boice JA, Hardwick JS, Beckford E, Taylor A, Carides A, Roila F, Herrstedt J. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. J Clin Oncol. 2011 Apr 10;29(11):1495-501. doi: 10.1200/JCO.2010.31.7859. Epub 2011 Mar 7.</citation>
    <PMID>21383291</PMID>
  </reference>
  <reference>
    <citation>Lasseter KC, Gambale J, Jin B, Bergman A, Constanzer M, Dru J, Han TH, Majumdar A, Evans JK, Murphy MG. Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol. 2007 Jul;47(7):834-40. doi: 10.1177/0091270007301800. Epub 2007 May 24.</citation>
    <PMID>17525168</PMID>
  </reference>
  <reference>
    <citation>Aapro M, Fabi A, Nole F, Medici M, Steger G, Bachmann C, Roncoroni S, Roila F. Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Ann Oncol. 2010 May;21(5):1083-8. doi: 10.1093/annonc/mdp584. Epub 2010 Jan 15.</citation>
    <PMID>20080830</PMID>
  </reference>
  <reference>
    <citation>Ito Y, Tsuda T, Minatogawa H, Kano S, Sakamaki K, Ando M, Tsugawa K, Kojima Y, Furuya N, Matsuzaki K, Fukuda M, Sugae S, Ohta I, Arioka H, Tokuda Y, Narui K, Tsuboya A, Suda T, Morita S, Boku N, Yamanaka T, Nakajima TE. Placebo-Controlled, Double-Blinded Phase III Study Comparing Dexamethasone on Day 1 With Dexamethasone on Days 1 to 3 With Combined Neurokinin-1 Receptor Antagonist and Palonosetron in High-Emetogenic Chemotherapy. J Clin Oncol. 2018 Apr 1;36(10):1000-1006. doi: 10.1200/JCO.2017.74.4375. Epub 2018 Feb 14.</citation>
    <PMID>29443652</PMID>
  </reference>
  <reference>
    <citation>Geling O, Eichler HG. Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J Clin Oncol. 2005 Feb 20;23(6):1289-94. doi: 10.1200/JCO.2005.04.022.</citation>
    <PMID>15718327</PMID>
  </reference>
  <reference>
    <citation>Aapro M, Rugo H, Rossi G, Rizzi G, Borroni ME, Bondarenko I, Sarosiek T, Oprean C, Cardona-Huerta S, Lorusso V, Karthaus M, Schwartzberg L, Grunberg S. A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol. 2014 Jul;25(7):1328-1333. doi: 10.1093/annonc/mdu101. Epub 2014 Mar 5.</citation>
    <PMID>24603643</PMID>
  </reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>May 19, 2022</last_update_submitted>
  <last_update_submitted_qc>May 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>emesis</keyword>
  <keyword>aprepitant</keyword>
  <keyword>carboplatin</keyword>
  <keyword>chemotherapy-induced nausea and vomiting</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nausea</mesh_term>
    <mesh_term>Vomiting</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Ondansetron</mesh_term>
    <mesh_term>Aprepitant</mesh_term>
    <mesh_term>Fosaprepitant</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03237611
org study id: 2015-5109
nct id: NCT03237611
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study evaluates a simple one day prophylaxis of nausea and vomiting for patients who are
      getting carboplatin based chemotherapy. In addition to standard oral dexmethasone and oral
      ondansetrone, participants will be given a third neurokinin 1 (NK1) antagonist agent, either
      Aprepitant or Fosaprepitant (they have been shown to be equally effective) to improve
      prevention of nausea and vomiting. No medications need to be taken beyond day 1.
Main predictive factor for the development of CINV is the emetic potential of a given
      chemotherapeutic agent. Carboplatin causes both acute and delayed emesis. Guideline groups
      have typically classified this agent as moderately emetic (MEC); however, its risk of
      inducing vomiting is at the upper range of this classification, and borders on highly emetic.
      The recommendation for prevention has been the use of a two-drug regimen (a
      5-hydroxytryptamine receptor antagonist (5-HT3RA) plus dexamethasone). The recent randomized
      studies have shown that patients given only a 2-drug regimen have about a 50% likelihood of
      emesis if they are women, and about a 30% likelihood of emesis if they are men. Major
      improvements were reported when a neurokinin-1 receptor antagonist (NK1RA) aprepitant was
      added. This improvement is of a similar magnitude to that seen in patients receiving
      cisplatin. Similar improvements were also seen in a trial in which the NK1RA antiemetic was
      rolapitant rather than aprepitant. The Tanioka and Yahata studies were conducted entirely in
      patients with GYN malignancies, and it is not surprising that the control rates are lower in
      these all female groups.

      The most commonly used NK1RA, aprepitant, is generally given over 3 days. Most studies
      indicate that this class of agent gives similar results when given in just one day, or over
      multiple days. Recent studies conducted by Roila compared the efficacy of aprepitant on day 1
      at a low dose (125 mg) versus the full three day regimen totaling 285 mg in patients
      receiving either cisplatin or the combination of anthracyclines plus cyclophosphamide (AC).
      In both studies, those patients randomly assigned to just one day of lower dose aprepitant
      had control of emesis equal to those receiving multiple days. In both of these trials,
      patients assigned to the single day aprepitant arm also received additional antiemetics on
      days 2 and 3. However, recent studies have failed to show an advantage for continuing
      dexamethasone after day 1 in patients receiving AC (14) or in those receiving cisplatin.
      Additionally, a meta-analysis indicated that as long as dexamethasone is given on day 1,
      there is no advantage to adding a serotonin antagonist (such as ondansetron) after day 1, and
      ondansetron has been shown to be similar to metoclopramide in the delayed emesis phase.
      Similarly to studies conducted by Roila, Grunberg and colleagues showed non-inferiority of
      single-dose intravenous (IV) fosaprepitant (a phosphorylated analog of aprepitant that is
      rapidly converted to aprepitant after IV administration) in a randomized study of patients
      receiving cisplatin chemotherapy. Fosaprepitant 115 mg IV has been approved as an alternative
      to the 125-mg oral aprepitant dose on day 1 of a 3-day regimen.

      There is very little data regarding the efficacy of continued steroids after day 1 in
      patients receiving carboplatin. Recent trials fail to show benefit for continuing
      dexamethasone after the day of chemotherapy. Aapro and colleagues in a 300 patient trial,
      showed that dexamethasone in combination with a 5-HT3RA on day 1 gave similar CINV protection
      to a multiple-day dexamethasone. Similarly, a Japanese study showed no difference in
      antiemetic efficacy of a single day dexamethasone regimen when prospectively compared with a
      3 day dexamethasone regimen; however, the 1 day regimen found significant reductions in
      steroid induced side effects. Additionally, a large multinational trial in patients receiving
      AC chemotherapy showed that a single dose of dexamethasone on day 1 along with a single day
      of NEPA (combination of 5-HT3RA palonosetron with NK1RA netupitant) offers convenient
      single-day prophylaxis for both acute and delayed CINV.

      Guideline groups are now starting to recommend a 3-agent preventive antiemetic regimen for
      patients receiving carboplatin, based on the evidence from the studies discussed above.
      However, not all guideline groups have yet made this recommendation. If it can be shown that
      a less expensive, more convenient (1-time administration), and potentially safer regimen
      performs in the same way for patients receiving carboplatin as it did for those receiving
      cisplatin or AC chemotherapy, and similarly to those receiving 3 days of aprepitant with
      carboplatin in the recent randomized trials, a new standard may be established.

      Objectives. Primary: To determine in patients receiving their first cycle of
      carboplatin-based chemotherapy, the complete control rate of emesis (acute and delayed; no
      vomiting and no use of rescue medications) with the addition of one dose of the oral
      aprepitant or intravenous fosaprepitant to a combination of oral dexamethasone + an oral
      5-HT3RA (ondansetron).

      Secondary: To estimate the control rate on the second cycle of this chemotherapy in those
      patients agreeing to be assessed in the subsequent chemotherapy cycle.

      Methods. CINV will be assessed by using the validated MASCC Antisemitism Tool (MAT), which
      efficiently evaluates the incidence of vomiting and the severity of nausea and vomiting in
      the acute and delayed emesis periods. Patients will be enrolled at Montefiore Medical Center
      and at Jacobi Medical Center. Patients will be asked to sign an informed consent form.
      Patients will be called on day 2 and 5 to remind about form completion, and will return the
      MAT form on their next outpatient visit (or immediately after completion if the patient is an
      inpatient). Consent forms then will be kept at a clinical trial center in a file. Case report
      forms were developed to capture data relevant to research.

      Antiemetic Medication administration. Serious adverse events are not expected since a lower
      dose and frequency of FDA approved medications will be given. They may be obtained or
      dispensed either by the Jacobi Medical Center, or the Montefiore Medical Center pharmacies,
      or aprepitant may be obtained by prescription from an outside pharmacy. If aprepitant is
      obtained at an outside pharmacy, the patient will bring the agent to their chemotherapy
      appointment; all NK1RA drug administration will be directly observed. The use of either
      aprepitant or fosaprepitant will be entirely the choice of the ordering oncologist, as both
      agents are equivalent. Ideally all drugs will be given immediately before (within 5 minutes)
      chemotherapy; however if a delay occurs up to 2 hours between the antiemetics and
      chemotherapy, this will be allowable and no additional dosing will be needed. The time of
      administration of the NK1RA in relation to the chemotherapy will be recorded.

      All patients will be given 125 mg of aprepitant orally or 115 mg IV of fosaprepitant prior to
      the first cycle of carboplatin-based chemotherapy.

      Antiemetic drug doses and schedules (same doses in all age and gender groups). Aprepitant or
      Fosaprepitant: 125 mg of Aprepitant orally immediately prior to chemotherapy. If
      fosaprepitant given instead, it will be administered immediately prior to chemotherapy at
      115mg IV (over 20 min). The administration site of the fosaprepitant will be noted and will
      be evaluated for possible venous irritation.

      Dexamethasone: 20 mg orally immediately prior to chemotherapy. Ondansetron: 16 mg orally,
      immediately prior to the chemotherapy.

      Patients agreeing to be followed on the second cycle with be assessed in the same way. During
      the follow-up visit after the first cycle, patients on study will be asked if they wish to
      continue participation during their second chemotherapy cycle (given that they are still
      eligible). Patients will not need to sign a separate consent, but will need to give their
      verbal affirmation, which will be noted in the case report form. The dosing and timing of the
      antiemetics may change according to the results in the first cycle, and other demographic
      characteristics, as follows:

      Female patients:

        -  If there was no vomiting on the first cycle and the antiemetics were well tolerated, all
           antiemetics will be given identically to cycle 1.

        -  If any vomiting was experienced on the first cycle, patients will instead receive the
           typical 3-day aprepitant (125 mg po day 1, and 80 mg po days 2 and 3), or fosaprepitant
           150 mg IV (given over 30 minutes) on day 1 only. (The choice of the aprepitant or
           fosaprepitant regimen will be at the discretion of the ordering oncologist). Ondansetron
           and dexamethasone will be given as on cycle 1. Additionally, 12mg of dexamethasone will
           be given on day 3

      Male patients:

        -  For those aged 50 or older, if there was no vomiting with the first cycle and the
           antiemetics were well tolerated, all antiemetics will be given identically to cycle1
           except that the aprepitant dose will be reduced to one 80 mg oral administration on day
           1. If fosaprepitant is used, it will be given at a total dose of 75 mg over 15 minutes.
           All will be given immediately prior to chemotherapy. Ondansetron and dexamethasone will
           be given as with cycle1.

        -  For those under age 50, if there was no vomiting on the first cycle and the antiemetics
           were well tolerated, all antiemetics will be given identically to cycle1.

        -  Male patients of any age, if they experienced any vomiting on the first cycle, will
           instead receive the typical 3-day aprepitant (125 mg po day 1, and 80 mg po days 2 and
           3), or fosaprepitant 150 mg IV (given over 30 minutes) on day 1 only. (The choice of the
           aprepitant or fosaprepitant regimen will be at the discretion of the ordering
           oncologist). Ondansetron and dexamethasone will be given as on cycle1. Additionally,
           12mg of dexamethasone will be given on day 3.

      Statistics and Analysis: The investigators will compute the relevant proportions and
      corresponding 95% confidence interval. The association of emesis control rate by gender and
      other socio-demographic and clinical covariates will be examined using Chi-square test, in
      case of small sample size Fisher's exact test will be used. Similar analysis will be
      performed to examine the secondary endpoints of complete control, complete emesis control and
      complete nausea control in the acute emesis period (first 24 hours after chemotherapy),
      delayed emesis period (24 - 120 hour period after chemotherapy) and in the control in the
      second cycle of chemotherapy.

      Justification of sample size: The investigators anticipate to recruit a total of 50 patients
      over one year after protocol approval, from prior experience with usage of carboplatin, the
      investigators expect approximately 60% will be females. The investigators project
      conservatively a 70% complete control rate based on prior literature (i.e. a 62% complete
      control rate in women and an 82% complete control rate in men). To evaluate the adequacy of
      the sample size (i.e. number of emesis control observed), precision was computed, as measured
      by the width of the 95% CI, with which the proportion of emesis control rate can be
      estimated. The width of the 95% CI will be no greater than 26.7% (i.e. +/-the lower and upper
      limit of complete control rate will be 55.4% to 82.1%) with the proposed sample size based on
      exact Clopper-Pearson formula.

      Data and Safety Monitoring Board (DSMB) will be the primary data monitoring and safety group.
      Information required in reports by this committee will include 1) summaries of accrual rates
      and patterns; 2) information on all adverse events and protocol violations; and 3) efficacy
      results at the time of each DSMB meeting, which will not be available to the investigators.
      Note, there is no interim analysis specified for this trial. This committee will meet at
      least annually. The majority of the members will not be from any of the study institutions,
      and no member will be involved in any way with the study. Membership will include as a
      minimum: a statistician, a medical oncologist, and a research oncology nurse.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Patient scheduled for the first cycle of carboplatin-based chemotherapy will be offered to receive 125mg of oral aprepitant or 115mg of fosaprepitant intravenously for prevention of chemotherapy-induced nausea and vomiting
primary purpose: Treatment
masking: None (Open Label)
measure: Complete control rate of emesis (this is a composite single endpoint which is commonly used in emesis trials. It encompasses no vomiting and no use of rescue medicines over a total 5-day period)
time frame: Complete control rate over the 5 day period after chemotherapy
description: Treatment efficacy will be determined by measuring complete control rate of emesis based on the visual scale analogue for emesis control, scored by patient from 0 to 10 (MAT form - MASCC Antiemesis Tool)
measure: Complete control of emesis
time frame: Complete control rate of emesis will be assessed on day 1 and 5 (both acute and delayed)
description: To estimate the control rate on the second cycle of this chemotherapy in those patients agreeing to be assessed in the subsequent chemotherapy cycle.
arm group label: low dose aprepitant or fosaprepitant
arm group type: Experimental
description: In addition to standard prophylactic antiemetics (Ondansetron 16mg and Dexamethasone 20mg) patients will be given aprepitant 125mg orally or 115mg fosaprepitant intravenously prior to the first cycle of carboplatin-based chemotherapy. No medications will be given afterwards
intervention type: Drug
intervention name: Aprepitant 125 mg
description: Patient scheduled for the first cycle of carboplatin-based chemotherapy will be offered to receive low doses of aprepitant (125mg of oral aprepitant) or 115mg of fosaprepitant intravenously for prevention of chemotherapy-induced nausea and vomiting
arm group label: low dose aprepitant or fosaprepitant
intervention type: Drug
intervention name: Fosaprepitant 115 MG
description: Patient scheduled for the first cycle of carboplatin-based chemotherapy will be offered to receive low doses of aprepitant (125mg of oral aprepitant) or 115mg of fosaprepitant intravenously for prevention of chemotherapy-induced nausea and vomiting
arm group label: low dose aprepitant or fosaprepitant
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone will be given as a part of standard CINV prophylaxis for patients receiving carboplatin-based chemotherapy, dosed at 20mg on day 1 of chemotherapy
arm group label: low dose aprepitant or fosaprepitant
intervention type: Drug
intervention name: Ondansetron 16 MG
description: Ondansetron will be given as a part of standard CINV prophylaxis for patients receiving carboplatin-based chemotherapy, dosed at 16mg on day 1 of chemotherapy
arm group label: low dose aprepitant or fosaprepitant
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Richard Gralla, MD
role: Principal Investigator
affiliation: Albert Einstein College of Medicine
facility: 
facility: 
country: United States
url: http://www.mascc.org
description: MASCC Antiemetic tool (MAT)
citation: Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med. 2008 Jun 5;358(23):2482-94. doi: 10.1056/NEJMra0706547. No abstract available.
PMID: 18525044
citation: Roila F, Herrstedt J, Aapro M, Gralla RJ, Einhorn LH, Ballatori E, Bria E, Clark-Snow RA, Espersen BT, Feyer P, Grunberg SM, Hesketh PJ, Jordan K, Kris MG, Maranzano E, Molassiotis A, Morrow G, Olver I, Rapoport BL, Rittenberg C, Saito M, Tonato M, Warr D; ESMO/MASCC Guidelines Working Group. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol. 2010 May;21 Suppl 5:v232-43. doi: 10.1093/annonc/mdq194. No abstract available.
PMID: 20555089
citation: NCCN Guidelines, Antiemesis, Version I.2015
citation: Tanioka M, Kitao A, Matsumoto K, Shibata N, Yamaguchi S, Fujiwara K, Minami H, Katakami N, Morita S, Negoro S. A randomised, placebo-controlled, double-blind study of aprepitant in nondrinking women younger than 70 years receiving moderately emetogenic chemotherapy. Br J Cancer. 2013 Aug 20;109(4):859-65. doi: 10.1038/bjc.2013.400. Epub 2013 Jul 16.
PMID: 23860530
citation: Ito Y, Karayama M, Inui N, Kuroishi S, Nakano H, Nakamura Y, Yokomura K, Toyoshima M, Shirai T, Masuda M, Yamada T, Yasuda K, Hayakawa H, Suda T, Chida K. Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy. Lung Cancer. 2014 Jun;84(3):259-64. doi: 10.1016/j.lungcan.2014.03.017. Epub 2014 Mar 27.
PMID: 24746177
citation: Yahata H, et al. Ann Oncol. 25 (Suppl 4): abstract 1481PD, 2014
citation: Gralla R, Jordan K, Rapoport B et al. Assessing the magnitude of antiemetic benefit with the addition of the NK1 receptor antagonist (NK1) aprepitant for all platinum agents: analysis of 1,872 patients (pts) in prospective randomized clinical phase III trials (RCTs) [abstract9057]. J Clin Oncol 2010; 28: 9057.
citation: Hesketh PJ, et al. Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in moderately emetogenic therapy (MEC). J Clin Oncol 33 (Suppl): abstract 9622, 2015
citation: Navari RM, Reinhardt RR, Gralla RJ, Kris MG, Hesketh PJ, Khojasteh A, Kindler H, Grote TH, Pendergrass K, Grunberg SM, Carides AD, Gertz BJ. Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. L-754,030 Antiemetic Trials Group. N Engl J Med. 1999 Jan 21;340(3):190-5. doi: 10.1056/NEJM199901213400304.
PMID: 9917226
citation: Roila F, Ruggeri B, Ballatori E, Fatigoni S, Caserta C, Licitra L, Mirabile A, Ionta MT, Massidda B, Cavanna L, Palladino MA, Tocci A, Fava S, Colantonio I, Angelelli L, Ciuffreda L, Fasola G, Zerilli F. Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study. Ann Oncol. 2015 Jun;26(6):1248-1253. doi: 10.1093/annonc/mdv132. Epub 2015 Mar 5.
PMID: 25743855
citation: Roila F, Ruggeri B, Ballatori E, Del Favero A, Tonato M. Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed emesis in patients with breast cancer: a randomized double-blind study. J Clin Oncol. 2014 Jan 10;32(2):101-6. doi: 10.1200/JCO.2013.51.4547. Epub 2013 Dec 9.
PMID: 24323030
citation: Grunberg S, Chua D, Maru A, Dinis J, DeVandry S, Boice JA, Hardwick JS, Beckford E, Taylor A, Carides A, Roila F, Herrstedt J. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. J Clin Oncol. 2011 Apr 10;29(11):1495-501. doi: 10.1200/JCO.2010.31.7859. Epub 2011 Mar 7.
PMID: 21383291
citation: Lasseter KC, Gambale J, Jin B, Bergman A, Constanzer M, Dru J, Han TH, Majumdar A, Evans JK, Murphy MG. Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol. 2007 Jul;47(7):834-40. doi: 10.1177/0091270007301800. Epub 2007 May 24.
PMID: 17525168
citation: Aapro M, Fabi A, Nole F, Medici M, Steger G, Bachmann C, Roncoroni S, Roila F. Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Ann Oncol. 2010 May;21(5):1083-8. doi: 10.1093/annonc/mdp584. Epub 2010 Jan 15.
PMID: 20080830
citation: Ito Y, Tsuda T, Minatogawa H, Kano S, Sakamaki K, Ando M, Tsugawa K, Kojima Y, Furuya N, Matsuzaki K, Fukuda M, Sugae S, Ohta I, Arioka H, Tokuda Y, Narui K, Tsuboya A, Suda T, Morita S, Boku N, Yamanaka T, Nakajima TE. Placebo-Controlled, Double-Blinded Phase III Study Comparing Dexamethasone on Day 1 With Dexamethasone on Days 1 to 3 With Combined Neurokinin-1 Receptor Antagonist and Palonosetron in High-Emetogenic Chemotherapy. J Clin Oncol. 2018 Apr 1;36(10):1000-1006. doi: 10.1200/JCO.2017.74.4375. Epub 2018 Feb 14.
PMID: 29443652
citation: Geling O, Eichler HG. Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J Clin Oncol. 2005 Feb 20;23(6):1289-94. doi: 10.1200/JCO.2005.04.022.
PMID: 15718327
citation: Aapro M, Rugo H, Rossi G, Rizzi G, Borroni ME, Bondarenko I, Sarosiek T, Oprean C, Cardona-Huerta S, Lorusso V, Karthaus M, Schwartzberg L, Grunberg S. A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol. 2014 Jul;25(7):1328-1333. doi: 10.1093/annonc/mdu101. Epub 2014 Mar 5.
PMID: 24603643
responsible party type: Sponsor
mesh term: Nausea
mesh term: Vomiting
mesh term: Dexamethasone
mesh term: Ondansetron
mesh term: Aprepitant
mesh term: Fosaprepitant
sharing ipd: No