Clinical Trials /

5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab

NCT03300609

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 3C-16-6
  • SECONDARY ID: NCI-2017-01414
  • SECONDARY ID: 3C-16-6
  • SECONDARY ID: P30CA014089
  • NCT ID: NCT03300609

Conditions

  • Colorectal Adenocarcinoma
  • RAS Wild Type
  • Stage III Colorectal Cancer AJCC v7
  • Stage IIIA Colorectal Cancer AJCC v7
  • Stage IIIB Colorectal Cancer AJCC v7
  • Stage IIIC Colorectal Cancer AJCC v7
  • Stage IV Colorectal Cancer AJCC v7
  • Stage IVA Colorectal Cancer AJCC v7
  • Stage IVB Colorectal Cancer AJCC v7

Interventions

DrugSynonymsArms
Panitumumab339177-26-3, ABX-EGF, ABX-EGF Monoclonal Antibody, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, VectibixArm I (panitumumab, leucovorin calcium, fluorouracil)
Oxaliplatin1-OHP, 266046, 61825-94-3, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, oxalato (1R,2R-cyclohexanediamine)platinum(II), oxalato (trans-l-1,2-diaminocyclohexane)platinum(II), Oxalatoplatin, Oxalatoplatinum, RP-54780, SR-96669, trans-l DACH oxalatoplatinum, trans-l diaminocyclohexane oxalatoplatinumArm I (panitumumab, leucovorin calcium, fluorouracil)
Leucovorin Calcium1492-18-8, 5-Formyl Tetrahydrofolate, 5-Formyl-5,6,7,8-tetrahydrofolic Acid, 5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic Acid, Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Fusilev, Lederfolat, Lederfolin, Leucosar, Rescufolin, Rescuvolin, Tonofolin, WellcovorinArm I (panitumumab, leucovorin calcium, fluorouracil)
Fluorouracil19893, 2,4-Dioxo-5-fluoropyrimidine, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluoro-2,4(1H,3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, 51-21-8, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757Arm I (panitumumab, leucovorin calcium, fluorouracil)
Capecitabine154361-50-9, 5'-Deoxy-5-fluoro-N-[(pentyloxy)carbonyl]-cytidine, 712807, Ro 09-1978/000, XelodaArm II (capecitabine)

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (panitumumab, leucovorin calcium, fluorouracil)ExperimentalINDUCTION 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.
  • Panitumumab
  • Oxaliplatin
  • Leucovorin Calcium
  • Fluorouracil
Arm II (capecitabine)Active ComparatorINDUCTION 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.
  • Panitumumab
  • Oxaliplatin
  • Leucovorin Calcium
  • Fluorouracil
  • Capecitabine

Eligibility Criteria

        Inclusion Criteria:

          -  Metastatic or locally advanced (unresectable) colorectal cancer with histological
             confirmation of adenocarcinoma (patients with or without measurable disease by imaging
             are eligible)

          -  No prior systemic chemotherapy for metastatic disease; subjects who received adjuvant
             therapy with FOLFOX and at the time of recurrence are at least 6 months away from last
             chemotherapy are eligible for this study

          -  At the time of randomization to maintenance therapy only patients who didn't progress
             by Response Evaluation Criteria in Solid Tumors (RECIST) criteria are eligible;
             patients with complete response (CR) and those who are candidates for resection will
             not be eligible for randomization to maintenance therapy, subjects who undergo surgery
             potentially have curable disease with defined duration of treatment and use of EGFR in
             the adjuvant setting is deemed to be detrimental in these population; likelihood of
             achieving CR is low and standard of care in this unique patient population is not well
             defined

          -  Provide written informed consent

          -  RAS wild‐type tumor

          -  Negative serum or urine pregnancy test done =< 7 days prior to registration, for women
             of childbearing potential only

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0 or 1

          -  Total serum bilirubin =< institutional upper limit of normal (ULN)

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin >= 9.0 g/dL (hemoglobin may be supported by transfusion)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5
             x ULN for subjects with liver involvement of their cancer)

          -  Creatinine within institutional limits of normal OR creatinine clearance > 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Magnesium >= lower limit of normal

          -  Willing to provide tissue and blood samples for mandatory correlative and research
             purposes

        Exclusion Criteria:

          -  Patients who are candidates for upfront metastasectomy (defined as those with limited
             liver metastatic disease) are not eligible for this study; the candidacy for
             resectability can be determined by the treating physician and or local surgeon; in
             ambiguous situations, please discuss the case with the principle investigator (PI)

          -  Known or suspected brain or central nervous system (CNS) metastases

          -  Active, uncontrolled infection, including hepatitis B, hepatitis C

          -  Patients with history of interstitial lung disease/pulmonary fibrosis

          -  Concurrent anti‐cancer therapy, including chemotherapy agents, targeted agents, or
             biological agents not otherwise specified in this protocol

          -  Radiation therapy =< 2 weeks prior to randomization

          -  Any of the following

               -  Pregnant or nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co‐morbid systemic illnesses or other severe concurrent disease, history of any
             psychiatric or addictive disorder, or laboratory abnormality, which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Patients known to be human immunodeficiency virus (HIV) positive

          -  Uncontrolled intercurrent illness whom in the opinion of the investigator, may
             increase the risks associated with study participation or study treatment, or may
             interfere with the conduct of the study or the interpretation of the study results

          -  Receiving any other investigational agent, which would be considered as a treatment
             for the primary neoplasm

          -  Other active malignancy =< 3 years prior to registration; exceptions are: nonmelanoma
             skin cancer or carcinoma‐in‐situ of the cervix that has been treated

          -  History of prior malignancy for which patient is receiving other specific treatment
             for their cancer

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to study drugs
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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.
Safety Issue:
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.

Secondary Outcome Measures

Measure:Treatment Response
Time Frame:Up to 4 years
Safety Issue:
Description:Response will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Southern California

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