<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/NCT03300609</url>
  </required_header>
  <id_info>
    <org_study_id>3C-16-6</org_study_id>
    <secondary_id>NCI-2017-01414</secondary_id>
    <secondary_id>3C-16-6</secondary_id>
    <secondary_id>P30CA014089</secondary_id>
    <nct_id>NCT03300609</nct_id>
  </id_info>
  <brief_title>5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab</brief_title>
  <official_title>Randomized Phase III Trial of 5-FU Based Maintenance Therapy With or Without Panitumumab in Patients With RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX + Panitumumab</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Southern California</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 randomized trial studies how well panitumumab, leucovorin calcium, and fluorouracil&#xD;
      after combination chemotherapy and panitumumab induction work in treating patients with RAS&#xD;
      wild type colorectal cancer that has spread from where it started to nearby tissue or lymph&#xD;
      nodes or other places in the body or cannot be removed by surgery. Monoclonal antibodies,&#xD;
      such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Drugs&#xD;
      used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in&#xD;
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping&#xD;
      them from dividing, or by stopping them from spreading. Giving panitumumab, leucovorin&#xD;
      calcium, and fluorouracil after combination chemotherapy and panitumumab induction may work&#xD;
      better in treating patients with colorectal cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the duration of progression free survival 1 (PFS1) in patients with RAS wild&#xD;
      type who have received induction leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) +&#xD;
      panitumumab and not progressed at 6 cycles and randomized to maintenance therapy with&#xD;
      fluorouracil (5FU) based therapy with or without panitumumab.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the response rate (RR) in patients with RAS wild type who are randomized to&#xD;
      maintenance therapy with 5FU based therapy to those randomized to 5FU based therapy with&#xD;
      panitumumab.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. Progress free survival 2 (PFS2). II. To assess the adverse event (AE) profile and safety&#xD;
      of the proposed treatment in this population.&#xD;
&#xD;
      III. To assess and compare the overall survival (OS) between the two treatment groups.&#xD;
&#xD;
      IV. To compare the quality of life (QOL) as measured by health state index (HIS) between&#xD;
      patients who achieve partial response (PR) versus (vs.) those who progress and those who have&#xD;
      stable disease during the induction phase.&#xD;
&#xD;
      V. To compare the QOL as measured by HSI between the two groups randomized to maintenance&#xD;
      therapy.&#xD;
&#xD;
      VI. To assess the evolution of RAS mutation under treatment during induction phase as well as&#xD;
      maintenance.&#xD;
&#xD;
      VII. To explore relationship between genomic and proteomic alterations of the tumor with&#xD;
      response and PFS to panitumumab.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      INDUCTION:&#xD;
&#xD;
      Patients receive panitumumab intravenously (IV) over 30-60 minutes, oxaliplatin IV over 2&#xD;
      hours, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Treatment repeats&#xD;
      every 14 days for up to 6 courses in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      MAINTENANCE: Patients who are not candidates for surgery, have no disease progression, or do&#xD;
      not have complete response after Induction are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients receive panitumumab IV over 30 minutes, leucovorin calcium IV, and&#xD;
      fluorouracil over 46-48 hours on day 1. Courses repeat every 14 days in the absence of&#xD;
      disease progression or unacceptable toxicity.&#xD;
&#xD;
      ARM II: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-21. Courses&#xD;
      repeat every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Insufficient Accrual&#xD;
  </why_stopped>
  <start_date type="Actual">February 27, 2018</start_date>
  <completion_date type="Actual">October 3, 2019</completion_date>
  <primary_completion_date type="Actual">October 3, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival 1</measure>
    <time_frame>From the date of randomization to the date of 1st documented disease progression or death due to any cause, whichever occurs first, assessed up to 7 months.</time_frame>
    <description>Disease progression will be determined by comparing tumor measurement during maintenance therapy to baseline measurement before starting maintenance treatment using Response Evaluation Criteria in Solid Tumors 1.1. will be conducted based on the intent-to-treat population from the time of randomization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment Response</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Response will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Colorectal Adenocarcinoma</condition>
  <condition>RAS Wild Type</condition>
  <condition>Stage III Colorectal Cancer AJCC v7</condition>
  <condition>Stage IIIA Colorectal Cancer AJCC v7</condition>
  <condition>Stage IIIB Colorectal Cancer AJCC v7</condition>
  <condition>Stage IIIC Colorectal Cancer AJCC v7</condition>
  <condition>Stage IV Colorectal Cancer AJCC v7</condition>
  <condition>Stage IVA Colorectal Cancer AJCC v7</condition>
  <condition>Stage IVB Colorectal Cancer AJCC v7</condition>
  <arm_group>
    <arm_group_label>Arm I (panitumumab, leucovorin calcium, fluorouracil)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INDUCTION Patients receive panitumumab IV over 30-60 minutes, oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.&#xD;
MAINTENANCE:&#xD;
Patients receive panitumumab IV over 30 minutes, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (capecitabine)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>INDUCTION Patients receive panitumumab IV over 30-60 minutes, oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.&#xD;
MAINTENANCE:&#xD;
Patients receive capecitabine PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Panitumumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (panitumumab, leucovorin calcium, fluorouracil)</arm_group_label>
    <arm_group_label>Arm II (capecitabine)</arm_group_label>
    <other_name>339177-26-3</other_name>
    <other_name>ABX-EGF</other_name>
    <other_name>ABX-EGF Monoclonal Antibody</other_name>
    <other_name>Clone E7.6.3</other_name>
    <other_name>MoAb ABX-EGF</other_name>
    <other_name>Monoclonal Antibody ABX-EGF</other_name>
    <other_name>Vectibix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (panitumumab, leucovorin calcium, fluorouracil)</arm_group_label>
    <arm_group_label>Arm II (capecitabine)</arm_group_label>
    <other_name>1-OHP</other_name>
    <other_name>266046</other_name>
    <other_name>61825-94-3</other_name>
    <other_name>Aiheng</other_name>
    <other_name>Dacotin</other_name>
    <other_name>Dacplat</other_name>
    <other_name>Diaminocyclohexane Oxalatoplatinum</other_name>
    <other_name>Eloxatin</other_name>
    <other_name>Eloxatine</other_name>
    <other_name>JM-83</other_name>
    <other_name>oxalato (1R,2R-cyclohexanediamine)platinum(II)</other_name>
    <other_name>oxalato (trans-l-1,2-diaminocyclohexane)platinum(II)</other_name>
    <other_name>Oxalatoplatin</other_name>
    <other_name>Oxalatoplatinum</other_name>
    <other_name>RP-54780</other_name>
    <other_name>SR-96669</other_name>
    <other_name>trans-l DACH oxalatoplatinum</other_name>
    <other_name>trans-l diaminocyclohexane oxalatoplatinum</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin Calcium</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (panitumumab, leucovorin calcium, fluorouracil)</arm_group_label>
    <arm_group_label>Arm II (capecitabine)</arm_group_label>
    <other_name>1492-18-8</other_name>
    <other_name>5-Formyl Tetrahydrofolate</other_name>
    <other_name>5-Formyl-5,6,7,8-tetrahydrofolic Acid</other_name>
    <other_name>5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic Acid</other_name>
    <other_name>Adinepar</other_name>
    <other_name>Calcifolin</other_name>
    <other_name>Calcium (6S)-Folinate</other_name>
    <other_name>Calcium Folinate</other_name>
    <other_name>Calcium Leucovorin</other_name>
    <other_name>Calfolex</other_name>
    <other_name>Calinat</other_name>
    <other_name>Cehafolin</other_name>
    <other_name>Citofolin</other_name>
    <other_name>Citrec</other_name>
    <other_name>Citrovorum Factor</other_name>
    <other_name>Cromatonbic Folinico</other_name>
    <other_name>Dalisol</other_name>
    <other_name>Disintox</other_name>
    <other_name>Divical</other_name>
    <other_name>Ecofol</other_name>
    <other_name>Emovis</other_name>
    <other_name>Flynoken A</other_name>
    <other_name>Folaren</other_name>
    <other_name>Folaxin</other_name>
    <other_name>FOLI-cell</other_name>
    <other_name>Foliben</other_name>
    <other_name>Folidan</other_name>
    <other_name>Folidar</other_name>
    <other_name>Folinac</other_name>
    <other_name>Folinate Calcium</other_name>
    <other_name>folinic acid</other_name>
    <other_name>Folinic Acid Calcium Salt Pentahydrate</other_name>
    <other_name>Folinoral</other_name>
    <other_name>Folinvit</other_name>
    <other_name>Foliplus</other_name>
    <other_name>Folix</other_name>
    <other_name>Fusilev</other_name>
    <other_name>Lederfolat</other_name>
    <other_name>Lederfolin</other_name>
    <other_name>Leucosar</other_name>
    <other_name>Rescufolin</other_name>
    <other_name>Rescuvolin</other_name>
    <other_name>Tonofolin</other_name>
    <other_name>Wellcovorin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorouracil</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (panitumumab, leucovorin calcium, fluorouracil)</arm_group_label>
    <arm_group_label>Arm II (capecitabine)</arm_group_label>
    <other_name>19893</other_name>
    <other_name>2,4-Dioxo-5-fluoropyrimidine</other_name>
    <other_name>5-Fluoro-2,4(1H, 3H)-pyrimidinedione</other_name>
    <other_name>5-Fluoro-2,4(1H,3H)-pyrimidinedione</other_name>
    <other_name>5-Fluorouracil</other_name>
    <other_name>5-Fluracil</other_name>
    <other_name>5-FU</other_name>
    <other_name>51-21-8</other_name>
    <other_name>AccuSite</other_name>
    <other_name>Carac</other_name>
    <other_name>Fluoro Uracil</other_name>
    <other_name>Fluouracil</other_name>
    <other_name>Flurablastin</other_name>
    <other_name>Fluracedyl</other_name>
    <other_name>Fluracil</other_name>
    <other_name>Fluril</other_name>
    <other_name>Fluroblastin</other_name>
    <other_name>Ribofluor</other_name>
    <other_name>Ro 2-9757</other_name>
    <other_name>Ro-2-9757</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm II (capecitabine)</arm_group_label>
    <other_name>154361-50-9</other_name>
    <other_name>5'-Deoxy-5-fluoro-N-[(pentyloxy)carbonyl]-cytidine</other_name>
    <other_name>712807</other_name>
    <other_name>Ro 09-1978/000</other_name>
    <other_name>Xeloda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (panitumumab, leucovorin calcium, fluorouracil)</arm_group_label>
    <arm_group_label>Arm II (capecitabine)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (panitumumab, leucovorin calcium, fluorouracil)</arm_group_label>
    <arm_group_label>Arm II (capecitabine)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metastatic or locally advanced (unresectable) colorectal cancer with histological&#xD;
             confirmation of adenocarcinoma (patients with or without measurable disease by imaging&#xD;
             are eligible)&#xD;
&#xD;
          -  No prior systemic chemotherapy for metastatic disease; subjects who received adjuvant&#xD;
             therapy with FOLFOX and at the time of recurrence are at least 6 months away from last&#xD;
             chemotherapy are eligible for this study&#xD;
&#xD;
          -  At the time of randomization to maintenance therapy only patients who didn't progress&#xD;
             by Response Evaluation Criteria in Solid Tumors (RECIST) criteria are eligible;&#xD;
             patients with complete response (CR) and those who are candidates for resection will&#xD;
             not be eligible for randomization to maintenance therapy, subjects who undergo surgery&#xD;
             potentially have curable disease with defined duration of treatment and use of EGFR in&#xD;
             the adjuvant setting is deemed to be detrimental in these population; likelihood of&#xD;
             achieving CR is low and standard of care in this unique patient population is not well&#xD;
             defined&#xD;
&#xD;
          -  Provide written informed consent&#xD;
&#xD;
          -  RAS wild-type tumor&#xD;
&#xD;
          -  Negative serum or urine pregnancy test done =&lt; 7 days prior to registration, for women&#xD;
             of childbearing potential only&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0 or 1&#xD;
&#xD;
          -  Total serum bilirubin =&lt; institutional upper limit of normal (ULN)&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500/mm^3&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/mm^3&#xD;
&#xD;
          -  Hemoglobin &gt;= 9.0 g/dL (hemoglobin may be supported by transfusion)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 2.5 x ULN (=&lt; 5&#xD;
             x ULN for subjects with liver involvement of their cancer)&#xD;
&#xD;
          -  Creatinine within institutional limits of normal OR creatinine clearance &gt; 60&#xD;
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal&#xD;
&#xD;
          -  Magnesium &gt;= lower limit of normal&#xD;
&#xD;
          -  Willing to provide tissue and blood samples for mandatory correlative and research&#xD;
             purposes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are candidates for upfront metastasectomy (defined as those with limited&#xD;
             liver metastatic disease) are not eligible for this study; the candidacy for&#xD;
             resectability can be determined by the treating physician and or local surgeon; in&#xD;
             ambiguous situations, please discuss the case with the principle investigator (PI)&#xD;
&#xD;
          -  Known or suspected brain or central nervous system (CNS) metastases&#xD;
&#xD;
          -  Active, uncontrolled infection, including hepatitis B, hepatitis C&#xD;
&#xD;
          -  Patients with history of interstitial lung disease/pulmonary fibrosis&#xD;
&#xD;
          -  Concurrent anti-cancer therapy, including chemotherapy agents, targeted agents, or&#xD;
             biological agents not otherwise specified in this protocol&#xD;
&#xD;
          -  Radiation therapy =&lt; 2 weeks prior to randomization&#xD;
&#xD;
          -  Any of the following&#xD;
&#xD;
               -  Pregnant or nursing women&#xD;
&#xD;
               -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
                  contraception&#xD;
&#xD;
          -  Co-morbid systemic illnesses or other severe concurrent disease, history of any&#xD;
             psychiatric or addictive disorder, or laboratory abnormality, which, in the judgment&#xD;
             of the investigator, would make the patient inappropriate for entry into this study or&#xD;
             interfere significantly with the proper assessment of safety and toxicity of the&#xD;
             prescribed regimens&#xD;
&#xD;
          -  Patients known to be human immunodeficiency virus (HIV) positive&#xD;
&#xD;
          -  Uncontrolled intercurrent illness whom in the opinion of the investigator, may&#xD;
             increase the risks associated with study participation or study treatment, or may&#xD;
             interfere with the conduct of the study or the interpretation of the study results&#xD;
&#xD;
          -  Receiving any other investigational agent, which would be considered as a treatment&#xD;
             for the primary neoplasm&#xD;
&#xD;
          -  Other active malignancy =&lt; 3 years prior to registration; exceptions are: nonmelanoma&#xD;
             skin cancer or carcinoma-in-situ of the cervix that has been treated&#xD;
&#xD;
          -  History of prior malignancy for which patient is receiving other specific treatment&#xD;
             for their cancer&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to study drugs&#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>Afsaneh Barzi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern California</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>USC/Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>September 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>June 8, 2020</last_update_submitted>
  <last_update_submitted_qc>June 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Calcium, Dietary</mesh_term>
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Folic Acid</mesh_term>
    <mesh_term>Formyltetrahydrofolates</mesh_term>
    <mesh_term>Tetrahydrofolates</mesh_term>
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Panitumumab</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Calcium</mesh_term>
    <mesh_term>Levoleucovorin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>November 17, 2021</submitted>
    <returned>December 16, 2021</returned>
  </pending_results>
  <!-- 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/NCT03300609
org study id: 3C-16-6
secondary id: NCI-2017-01414
secondary id: 3C-16-6
secondary id: P30CA014089
nct id: NCT03300609
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This randomized trial studies how well panitumumab, leucovorin calcium, and fluorouracil
      after combination chemotherapy and panitumumab induction work in treating patients with RAS
      wild type colorectal cancer that has spread from where it started to nearby tissue or lymph
      nodes or other places in the body or cannot be removed by surgery. Monoclonal antibodies,
      such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Drugs
      used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Giving panitumumab, leucovorin
      calcium, and fluorouracil after combination chemotherapy and panitumumab induction may work
      better in treating patients with colorectal cancer.
PRIMARY OBJECTIVES:

      I. To compare the duration of progression free survival 1 (PFS1) in patients with RAS wild
      type who have received induction leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) +
      panitumumab and not progressed at 6 cycles and randomized to maintenance therapy with
      fluorouracil (5FU) based therapy with or without panitumumab.

      SECONDARY OBJECTIVES:

      I. To compare the response rate (RR) in patients with RAS wild type who are randomized to
      maintenance therapy with 5FU based therapy to those randomized to 5FU based therapy with
      panitumumab.

      TERTIARY OBJECTIVES:

      I. Progress free survival 2 (PFS2). II. To assess the adverse event (AE) profile and safety
      of the proposed treatment in this population.

      III. To assess and compare the overall survival (OS) between the two treatment groups.

      IV. To compare the quality of life (QOL) as measured by health state index (HIS) between
      patients who achieve partial response (PR) versus (vs.) those who progress and those who have
      stable disease during the induction phase.

      V. To compare the QOL as measured by HSI between the two groups randomized to maintenance
      therapy.

      VI. To assess the evolution of RAS mutation under treatment during induction phase as well as
      maintenance.

      VII. To explore relationship between genomic and proteomic alterations of the tumor with
      response and PFS to panitumumab.

      OUTLINE:

      INDUCTION:

      Patients receive panitumumab intravenously (IV) over 30-60 minutes, oxaliplatin IV over 2
      hours, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Treatment repeats
      every 14 days for up to 6 courses in the absence of disease progression or unacceptable
      toxicity.

      MAINTENANCE: Patients who are not candidates for surgery, have no disease progression, or do
      not have complete response after Induction are randomized to 1 of 2 arms.

      ARM I: Patients receive panitumumab IV over 30 minutes, leucovorin calcium IV, and
      fluorouracil over 46-48 hours on day 1. Courses repeat every 14 days in the absence of
      disease progression or unacceptable toxicity.

      ARM II: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-21. Courses
      repeat every 21 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival 1
time frame: From the date of randomization to the date of 1st documented disease progression or death due to any cause, whichever occurs first, assessed up to 7 months.
description: Disease progression will be determined by comparing tumor measurement during maintenance therapy to baseline measurement before starting maintenance treatment using Response Evaluation Criteria in Solid Tumors 1.1. will be conducted based on the intent-to-treat population from the time of randomization.
measure: Treatment Response
time frame: Up to 4 years
description: Response will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1)
arm group label: Arm I (panitumumab, leucovorin calcium, fluorouracil)
arm group type: Experimental
description: INDUCTION Patients receive panitumumab IV over 30-60 minutes, oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE:
Patients receive panitumumab IV over 30 minutes, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II (capecitabine)
arm group type: Active Comparator
description: INDUCTION Patients receive panitumumab IV over 30-60 minutes, oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE:
Patients receive capecitabine PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Panitumumab
description: Given IV
arm group label: Arm I (panitumumab, leucovorin calcium, fluorouracil)
arm group label: Arm II (capecitabine)
other name: 339177-26-3
other name: ABX-EGF
other name: ABX-EGF Monoclonal Antibody
other name: Clone E7.6.3
other name: MoAb ABX-EGF
other name: Monoclonal Antibody ABX-EGF
other name: Vectibix
intervention type: Drug
intervention name: Oxaliplatin
description: Given IV
arm group label: Arm I (panitumumab, leucovorin calcium, fluorouracil)
arm group label: Arm II (capecitabine)
other name: 1-OHP
other name: 266046
other name: 61825-94-3
other name: Aiheng
other name: Dacotin
other name: Dacplat
other name: Diaminocyclohexane Oxalatoplatinum
other name: Eloxatin
other name: Eloxatine
other name: JM-83
other name: oxalato (1R,2R-cyclohexanediamine)platinum(II)
other name: oxalato (trans-l-1,2-diaminocyclohexane)platinum(II)
other name: Oxalatoplatin
other name: Oxalatoplatinum
other name: RP-54780
other name: SR-96669
other name: trans-l DACH oxalatoplatinum
other name: trans-l diaminocyclohexane oxalatoplatinum
intervention type: Drug
intervention name: Leucovorin Calcium
description: Given IV
arm group label: Arm I (panitumumab, leucovorin calcium, fluorouracil)
arm group label: Arm II (capecitabine)
other name: 1492-18-8
other name: 5-Formyl Tetrahydrofolate
other name: 5-Formyl-5,6,7,8-tetrahydrofolic Acid
other name: 5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic Acid
other name: Adinepar
other name: Calcifolin
other name: Calcium (6S)-Folinate
other name: Calcium Folinate
other name: Calcium Leucovorin
other name: Calfolex
other name: Calinat
other name: Cehafolin
other name: Citofolin
other name: Citrec
other name: Citrovorum Factor
other name: Cromatonbic Folinico
other name: Dalisol
other name: Disintox
other name: Divical
other name: Ecofol
other name: Emovis
other name: Flynoken A
other name: Folaren
other name: Folaxin
other name: FOLI-cell
other name: Foliben
other name: Folidan
other name: Folidar
other name: Folinac
other name: Folinate Calcium
other name: folinic acid
other name: Folinic Acid Calcium Salt Pentahydrate
other name: Folinoral
other name: Folinvit
other name: Foliplus
other name: Folix
other name: Fusilev
other name: Lederfolat
other name: Lederfolin
other name: Leucosar
other name: Rescufolin
other name: Rescuvolin
other name: Tonofolin
other name: Wellcovorin
intervention type: Drug
intervention name: Fluorouracil
description: Given IV
arm group label: Arm I (panitumumab, leucovorin calcium, fluorouracil)
arm group label: Arm II (capecitabine)
other name: 19893
other name: 2,4-Dioxo-5-fluoropyrimidine
other name: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
other name: 5-Fluoro-2,4(1H,3H)-pyrimidinedione
other name: 5-Fluorouracil
other name: 5-Fluracil
other name: 5-FU
other name: 51-21-8
other name: AccuSite
other name: Carac
other name: Fluoro Uracil
other name: Fluouracil
other name: Flurablastin
other name: Fluracedyl
other name: Fluracil
other name: Fluril
other name: Fluroblastin
other name: Ribofluor
other name: Ro 2-9757
other name: Ro-2-9757
intervention type: Drug
intervention name: Capecitabine
description: Given PO
arm group label: Arm II (capecitabine)
other name: 154361-50-9
other name: 5'-Deoxy-5-fluoro-N-[(pentyloxy)carbonyl]-cytidine
other name: 712807
other name: Ro 09-1978/000
other name: Xeloda
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Arm I (panitumumab, leucovorin calcium, fluorouracil)
arm group label: Arm II (capecitabine)
other name: Quality of Life Assessment
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (panitumumab, leucovorin calcium, fluorouracil)
arm group label: Arm II (capecitabine)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Afsaneh Barzi, MD
role: Principal Investigator
affiliation: University of Southern California
facility: 
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Calcium, Dietary
mesh term: Leucovorin
mesh term: Folic Acid
mesh term: Formyltetrahydrofolates
mesh term: Tetrahydrofolates
mesh term: Antineoplastic Agents, Immunological
mesh term: Panitumumab
mesh term: Fluorouracil
mesh term: Capecitabine
mesh term: Oxaliplatin
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Calcium
mesh term: Levoleucovorin
sharing ipd: Undecided
submitted: November 17, 2021
returned: December 16, 2021