<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/NCT03246074</url>
  </required_header>
  <id_info>
    <org_study_id>J1708</org_study_id>
    <secondary_id>IRB00110406</secondary_id>
    <nct_id>NCT03246074</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer</brief_title>
  <official_title>Phase I Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rigel Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research is being done to test the safety of the combination of the study drugs&#xD;
      fostamatinib and paclitaxel. This study tests different doses of the drugs to see which doses&#xD;
      are safest in people with ovaria cancer when given together.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase I, open-label, non-randomized multicenter dose-escalation study with the&#xD;
      primary objective to determine the maximally tolerated dose (MTD) of fostamatinib when&#xD;
      administered with weekly paclitaxel in women with recurrent platinum-resistant ovarian,&#xD;
      fallopian tube, or primary peritoneal cancer.&#xD;
&#xD;
      Between 8 and 18 adult female subjects will be enrolled and receive weekly paclitaxel in&#xD;
      combination with increasing doses of fostamatinib. There will be three dosing intervals of&#xD;
      fostamatinib (100 mg bid, 150 mg bid, and 200mg bid) selected based on prior phase I studies&#xD;
      of single agent fostamatinib. Dose-escalation will follow a modified toxicity probability&#xD;
      interval (mTPI) design. In this study, up to 18 adult female subjects will be enrolled and&#xD;
      receive weekly paclitaxel in combination with fostamatinib at the MTD of the combination; at&#xD;
      least 6 patients with receive fostamatinib plus paclitaxel at the MTD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 3, 2018</start_date>
  <completion_date type="Anticipated">October 1, 2024</completion_date>
  <primary_completion_date type="Actual">August 9, 2022</primary_completion_date>
  <phase>Phase 1</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>3.5 years</time_frame>
    <description>To determine the safety, tolerability, and maximum tolerated dose (MTD) of fostamatinib when administered in combination with weekly paclitaxel</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response rate of treatment with combination therapy</measure>
    <time_frame>3.5 years</time_frame>
    <description>To estimate the objective response rate in the study population treated with the combination of fostamatinib and paclitaxel</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival determination based on progression-free survival</measure>
    <time_frame>10 years</time_frame>
    <description>To estimate the progression-free survival in the study population treated with the combination of fostamatinib and paclitaxel</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug metabolism determination</measure>
    <time_frame>3.5 years</time_frame>
    <description>To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using Peak Plasma Concentration (Cmax in ng/mL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug metabolism determination</measure>
    <time_frame>3.5 years</time_frame>
    <description>To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using Area Under the Curve (AUC) (ng*hr/mL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug metabolism determination</measure>
    <time_frame>3.5 years</time_frame>
    <description>To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using half life (hours)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>Fostamatinib and Paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive paclitaxel on Days 1, 8 and 15 of each cycle and fostamatinib at a fixed oral dose twice daily throughout each 28-day cycle. The dose of fostamatinib will be determined by the enrollment dose level. Given the mTPI design, dose-escalation decisions will be made based on the three dosing intervals, where the underdosing interval corresponds to dose escalation (E), overdosing interval corresponds to dose de-escalation (D), and proper dosing corresponds to staying at the current dose (S). The initial dose level will be Level 1 of Table 1. Participants will be individually continually assessed for DLT. The associated dose-escalation decisions are presented in Table 2. For illustration, suppose a cohort of 3 patients is at the current dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fostamatinib and Paclitaxel</intervention_name>
    <description>Drug: Fostamatinib (oral; 100 mg, 150 mg, or 200 mg)&#xD;
Drug: Paclitaxel (60-80 mg/m2)</description>
    <arm_group_label>Fostamatinib and Paclitaxel</arm_group_label>
    <other_name>Fostamatinib and Abraxane</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  Inclusion Criteria&#xD;
&#xD;
               1. Patients must have histologically or cytologically confirmed epithelial ovarian,&#xD;
                  fallopian tube, or primary peritoneal carcinoma. Histologic documentation (via&#xD;
                  the pathology report) of the original primary tumor is required.&#xD;
&#xD;
               2. Patients must have measurable disease, according to RECIST v1.1.&#xD;
&#xD;
               3. Patients must have recurrent, platinum-resistant disease (defined as having&#xD;
                  relapsed within 6 months of last platinum-containing regimen) or be unable to&#xD;
                  receive further platinum therapy. There is no limit on the number of prior&#xD;
                  treatment regimens; however, patients may not have previously received weekly&#xD;
                  paclitaxel in the recurrent setting. Previous dose dense paclitaxel as initial&#xD;
                  therapy is allowable.&#xD;
&#xD;
               4. Patients must have the ability to take oral medications.&#xD;
&#xD;
               5. Females, age ≥18 years.&#xD;
&#xD;
               6. ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).&#xD;
&#xD;
               7. Life expectancy of greater than 3 months.&#xD;
&#xD;
               8. Patients must have normal organ and marrow function.&#xD;
&#xD;
               9. Patients with a diagnosis of hypertension are required to have adequate blood&#xD;
                  pressure control prior to enrollment, defined as blood pressure ≤ 140/90 mmHg.&#xD;
&#xD;
              10. The effects of fostamatinib on the developing human fetus are unknown. For this&#xD;
                  reason, women of childbearing potential must agree to use adequate contraception&#xD;
                  (hormonal or barrier method of birth control; abstinence) prior to study entry&#xD;
                  and for the duration of study participation. Should a woman become pregnant or&#xD;
                  suspect she is pregnant while she is participating in this study, she should&#xD;
                  inform her treating physician immediately.&#xD;
&#xD;
              11. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral&#xD;
                  therapy with undetectable viral load within 6 months are eligible for this trial&#xD;
                  if the anti-retroviral therapy is not an excluded concurrent medication.&#xD;
&#xD;
              12. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV&#xD;
                  viral load must be undetectable on suppressive therapy, if indicated and the&#xD;
                  suppressive therapy is not an excluded concurrent medication.&#xD;
&#xD;
              13. Patients with a history of hepatitis C virus (HCV) infection must have been&#xD;
                  treated and cured. For patients with HCV infection who are currently on&#xD;
                  treatment, they are eligible if they have an undetectable HCV viral load and the&#xD;
                  HCV therapy is not an excluded concurrent medication.&#xD;
&#xD;
              14. Patients with treated brain metastases are eligible if follow-up brain imaging&#xD;
                  after central nervous system (CNS)-directed therapy shows no evidence of&#xD;
                  progression.&#xD;
&#xD;
              15. Patients who are willing and able to comply with the protocol and study&#xD;
                  procedures.&#xD;
&#xD;
                  Tumor biopsy or paracentesis for tumor cells before therapy (at baseline) and&#xD;
                  after initiation of treatment (before Cycle 2) for at least 75% of subjects if&#xD;
                  this is clinically and safely feasible to do so. For patients who have had tumor&#xD;
                  tissue sampled within 6 months of enrollment and no intervening anti-neoplastic&#xD;
                  therapy, archived tissue may satisfy the requirement of the pre-treatment biopsy&#xD;
                  with permission of the protocol chair.&#xD;
&#xD;
              16. Patients with a prior or concurrent malignancy whose natural history or treatment&#xD;
                  does not have the potential to interfere with the safety or efficacy assessment&#xD;
                  of the investigational regimen are eligible for this trial, with permission of&#xD;
                  the protocol chair.&#xD;
&#xD;
              17. Patients with known history or current symptoms of cardiac disease, or history of&#xD;
                  treatment with cardiotoxic agents, should have a clinical risk assessment of&#xD;
                  cardiac function using the New York Heart Association Functional Classification.&#xD;
                  To be eligible for this trial, patients should be class 2B or better.&#xD;
&#xD;
              18. The effects of fostamatinib on the developing human fetus are unknown. For this&#xD;
                  reason and because spleen tyrosine kinase inhibitors as well as other therapeutic&#xD;
                  agents used in this trial are known to be teratogenic, women of child-bearing&#xD;
                  potential must agree to use adequate contraception (hormonal or barrier method of&#xD;
                  birth control; abstinence) prior to study entry and for the duration of study&#xD;
                  participation. Should a woman become pregnant or suspect she is pregnant while&#xD;
                  she or her partner is participating in this study, she should inform her treating&#xD;
                  physician immediately.&#xD;
&#xD;
              19. Ability to understand and the willingness to sign a written informed consent&#xD;
                  document.&#xD;
&#xD;
          -  Exclusion Criteria&#xD;
&#xD;
               1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for&#xD;
                  nitrosoureas or mitomycin C) prior to entering the study. Hormonal therapy&#xD;
                  directed at the malignant tumor must be discontinued at least one week prior to&#xD;
                  registration.&#xD;
&#xD;
               2. Patients who have not recovered (CTCAE v4.03 grade ≤1) from adverse events due to&#xD;
                  agents administered more than 4 weeks earlier, unless those events are deemed to&#xD;
                  have returned to baseline, are irreversible, or are unlikely to develop into a&#xD;
                  life-threatening condition at the permission of the Protocol Chair (e.g.,&#xD;
                  alopecia).&#xD;
&#xD;
               3. Patients who are currently receiving or have previously received any other&#xD;
                  investigational agents within 3 weeks prior to entering the study.&#xD;
&#xD;
               4. Patients with known untreated brain metastases, as progressive neurologic&#xD;
                  dysfunction may develop that would confound the evaluation of neurologic and&#xD;
                  other adverse events.&#xD;
&#xD;
               5. Patients with Grade 2 or greater neuropathy.&#xD;
&#xD;
               6. History of allergic reactions attributed to compounds of similar chemical or&#xD;
                  biologic composition to fostamatinib or paclitaxel. Patients who are able to&#xD;
                  tolerate paclitaxel on a desensitization protocol will be allowed.&#xD;
&#xD;
               7. Strong CYP3A4 inhibitors or inducers should not be used within 3 days of Day 1&#xD;
                  dosing until the end of study. Moderate CYP3A4 inhibitors or inducers should be&#xD;
                  used with caution.&#xD;
&#xD;
               8. Uncontrolled intercurrent illness&#xD;
&#xD;
               9. Pregnant women are excluded from this study because the potential for teratogenic&#xD;
                  or abortifacient effects of fostamatinib are unknown. Because there is an unknown&#xD;
                  but potential risk for adverse events in nursing infants secondary to treatment&#xD;
                  of the mother with fostamatinib, breastfeeding should be discontinued if the&#xD;
                  mother is treated with fostamatinib. These potential risks may also apply to&#xD;
                  other agents used in this study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Must have ovarian, fallopian tube or peritoneal carcinoma.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephanie Gaillard, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sibley Memorial Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania Health System</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 15, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase I</keyword>
  <keyword>Ovarian Cancer</keyword>
  <keyword>Fostamatinib and Paclitaxel</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual participant data will not be shared.</ipd_description>
  </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/NCT03246074
org study id: J1708
secondary id: IRB00110406
nct id: NCT03246074
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research is being done to test the safety of the combination of the study drugs
      fostamatinib and paclitaxel. This study tests different doses of the drugs to see which doses
      are safest in people with ovaria cancer when given together.
This is a phase I, open-label, non-randomized multicenter dose-escalation study with the
      primary objective to determine the maximally tolerated dose (MTD) of fostamatinib when
      administered with weekly paclitaxel in women with recurrent platinum-resistant ovarian,
      fallopian tube, or primary peritoneal cancer.

      Between 8 and 18 adult female subjects will be enrolled and receive weekly paclitaxel in
      combination with increasing doses of fostamatinib. There will be three dosing intervals of
      fostamatinib (100 mg bid, 150 mg bid, and 200mg bid) selected based on prior phase I studies
      of single agent fostamatinib. Dose-escalation will follow a modified toxicity probability
      interval (mTPI) design. In this study, up to 18 adult female subjects will be enrolled and
      receive weekly paclitaxel in combination with fostamatinib at the MTD of the combination; at
      least 6 patients with receive fostamatinib plus paclitaxel at the MTD.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events
time frame: 3.5 years
description: To determine the safety, tolerability, and maximum tolerated dose (MTD) of fostamatinib when administered in combination with weekly paclitaxel
measure: Response rate of treatment with combination therapy
time frame: 3.5 years
description: To estimate the objective response rate in the study population treated with the combination of fostamatinib and paclitaxel
measure: Survival determination based on progression-free survival
time frame: 10 years
description: To estimate the progression-free survival in the study population treated with the combination of fostamatinib and paclitaxel
measure: Drug metabolism determination
time frame: 3.5 years
description: To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using Peak Plasma Concentration (Cmax in ng/mL)
measure: Drug metabolism determination
time frame: 3.5 years
description: To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using Area Under the Curve (AUC) (ng*hr/mL)
measure: Drug metabolism determination
time frame: 3.5 years
description: To assess the drug metabolism of fostamatinib when combined with weekly paclitaxel using half life (hours)
arm group label: Fostamatinib and Paclitaxel
arm group type: Experimental
description: Participants will receive paclitaxel on Days 1, 8 and 15 of each cycle and fostamatinib at a fixed oral dose twice daily throughout each 28-day cycle. The dose of fostamatinib will be determined by the enrollment dose level. Given the mTPI design, dose-escalation decisions will be made based on the three dosing intervals, where the underdosing interval corresponds to dose escalation (E), overdosing interval corresponds to dose de-escalation (D), and proper dosing corresponds to staying at the current dose (S). The initial dose level will be Level 1 of Table 1. Participants will be individually continually assessed for DLT. The associated dose-escalation decisions are presented in Table 2. For illustration, suppose a cohort of 3 patients is at the current dose.
intervention type: Drug
intervention name: Fostamatinib and Paclitaxel
description: Drug: Fostamatinib (oral; 100 mg, 150 mg, or 200 mg)
Drug: Paclitaxel (60-80 mg/m2)
arm group label: Fostamatinib and Paclitaxel
other name: Fostamatinib and Abraxane
criteria: 
gender: Female
gender based: Yes
gender description: Must have ovarian, fallopian tube or peritoneal carcinoma.
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Stephanie Gaillard, MD
role: Principal Investigator
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Paclitaxel
sharing ipd: No
ipd description: Individual participant data will not be shared.