Clinical Trials /

Panitumumab and Chemotherapy in Patients With Advanced Colorectal Cancer After Prior Therapy With Bevacizumab

NCT01814501

Description:

This phase II trial studies how well panitumumab and combination chemotherapy works in treating patients with metastatic colorectal cancer previously treated with combination chemotherapy and bevacizumab. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panitumumab and combination chemotherapy together may kill more tumor cells

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Panitumumab and Chemotherapy in Patients With Advanced Colorectal Cancer After Prior Therapy With Bevacizumab
  • Official Title: A Phase II Study of Panitumumab in Combination With FOLFIRI After Progression on FOLFIRI Plus Bevacizumab in KRAS(Kirsten Rat Sarcoma) and NRAS Wild-Type Metastatic Colorectal Cancer.

Clinical Trial IDs

  • ORG STUDY ID: OSU-11131
  • SECONDARY ID: NCI-2013-00432
  • NCT ID: NCT01814501

Conditions

  • Mucinous Adenocarcinoma of the Colon
  • Mucinous Adenocarcinoma of the Rectum
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Signet Ring Adenocarcinoma of the Colon
  • Signet Ring Adenocarcinoma of the Rectum
  • Stage IV Colon Cancer
  • Stage IV Rectal Cancer

Interventions

DrugSynonymsArms
panitumumabABX-EGF, MOAB ABX-EGF, monoclonal antibody ABX-EGF, VectibixTreatment (panitumumab, combination chemotherapy)
irinotecan hydrochlorideCampto, Camptosar, CPT-11, irinotecan, U-101440ETreatment (panitumumab, combination chemotherapy)
fluorouracil5-fluorouracil, 5-Fluracil, 5-FUTreatment (panitumumab, combination chemotherapy)
leucovorin calciumCF, CFR, LVTreatment (panitumumab, combination chemotherapy)

Purpose

This phase II trial studies how well panitumumab and combination chemotherapy works in treating patients with metastatic colorectal cancer previously treated with combination chemotherapy and bevacizumab. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panitumumab and combination chemotherapy together may kill more tumor cells

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the median progression-free survival in patients treated with leucovorin
      calcium, fluorouracil, and irinotecan hydrochloride (FOLFIRI) and panitumumab for K-ras and
      NRAS wild-type, metastatic colorectal carcinoma who have already progressed on FOLFIRI +
      Bevacizumab.

      SECONDARY OBJECTIVES:

      I. To determine the frequency and severity of toxicities of the regimens. II. To determine
      overall response rate. III. To determine the median overall survival and the overall survival
      rate at 1 year.

      OUTLINE:

      Patients receive panitumumab intravenously (IV) over 60-90 minutes, leucovorin calcium IV
      over 90 minutes, fluorouracil IV continuously over 46 hours, and irinotecan hydrochloride IV
      over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up periodically.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (panitumumab, combination chemotherapy)Experimental5-Fluorouracil, irinotecan, and panitumumab
  • irinotecan hydrochloride
  • fluorouracil
  • leucovorin calcium

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with advanced adenocarcinoma of the colon or rectum not curable with surgery
             or radiotherapy and have been previously treated for their disease with FOLFIRI plus
             bevacizumab in the first line metastatic setting; patients will only be eligible if
             their last line of therapy prior to enrolling onto the study was FOLFIRI and
             bevacizumab received no more than 6 months prior to enrolling in this study; they
             should have been treated with FOLFIRI plus bevacizumab until disease progression is
             radiographically documented

          -  Patients' tumors will need to tested for the K-RAS and N-RAS mutation status; only
             those patients with wild-type or unmutated K-RAS and N-RAS oncogene are eligible to
             participate in this study

          -  Provide written informed consent prior to study-specific screening procedures, with
             the understanding that the patient has the right to withdraw from the study at any
             time, without prejudice

          -  Prior cetuximab is allowed in the adjuvant but not in the metastatic setting, but must
             have been completed at least 6 months before starting this trial

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1

          -  Life expectancy greater than 12 weeks

          -  No active brain metastasis; previously surgically treated or irradiated lesions are
             allowed if not clinically active

          -  Has a negative serum pregnancy test within 7 days prior to registration (female
             patients of childbearing potential)

          -  Ability to understand and willingness to sign a written informed consent

          -  No history of severe reactions to fluorouracil (5-FU), irinotecan (irinotecan
             hydrochloride), or a monoclonal antibody

          -  Leukocytes >= 3000/uL

          -  Absolute neutrophil count >= 1500/uL

          -  Platelets >= 100,000/uL

          -  Hemoglobin >= 9 mg/dL

          -  Total bilirubin =< 1.5 X upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 X ULN (or < 5 x
             ULN with liver metastases)

          -  Creatinine clearance (CrCl) >= 30 ml/min (Cockroft-Gault equation)

          -  Magnesium >= lower limit of normal

          -  Measurable disease is required according to Response Evaluation Criteria in Solid
             Tumors (RECIST) 1.1 criteria

          -  The effects of Panitumumab on the developing human fetus are unknown; for this reason
             and because monoclonal antibodies as well as other therapeutic agents used in this
             trial are known to be teratogenic, women of child-bearing potential and men must agree
             to use adequate contraception (hormonal or barrier method of birth control;
             abstinence) prior to study entry and for the duration of study participation and up to
             6 months after completing therapy; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

        Exclusion Criteria:

          -  Pregnant or lactating women; women of childbearing potential with either a positive or
             no pregnancy test at baseline; woman or men of childbearing potential not using a
             reliable and appropriate contraceptive method; (postmenopausal woman must have been
             amenorrheic for at least 12 months to be considered of non-childbearing potential)

          -  Sexually active males unwilling to practice contraception during the study and 6
             months beyond

          -  Uncontrolled intercurrent illness including but not limited to clinically significant
             cardiac disease not well controlled with medication (e.g. congestive heart failure,
             symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction
             within the last 12 months, and serious concurrent infections

          -  History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or
             evidence of interstitial lung disease on baseline chest computed tomography (CT) scan

          -  KRAS or NRAS mutant tumors

          -  Active inflammatory bowel disease or other bowel disease causing chronic diarrhea
             (defined as >= Common Toxicity Criteria [CTC] grade 2 [Common Terminology Criteria for
             Adverse Events (CTCAE) version 4.0])

          -  Clinically significant cardiovascular disease (including myocardial infarction,
             unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
             arrhythmia) =< 1 year

          -  Bevacizumab within the last 4 weeks before starting treatment on trial

          -  Patient is more than 6 months since the last dose of FOLFIRI

          -  Patients who have required toxicity related dose reductions of no less than 50% of the
             original dose of infusional 5-FU and/or irinotecan during the administration of
             FOLFIRI + bevacizumab

          -  Prior exposure to panitumumab in any setting

          -  Prior exposure to cetuximab in the metastatic (stage IV) setting

          -  Radiotherapy =< 14 days prior to enrollment; patients must have recovered from all
             radiotherapy-related toxicities

          -  Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity
             to 5-fluorouracil, leucovorin (leucovorin calcium), irinotecan, or panitumumab

          -  Treatment for other carcinomas within the last three years, except cured non-melanoma
             skin and treated in-situ cervical cancer

          -  Participation in any investigational drug study within 4 weeks preceding the start of
             study treatment

          -  Other serious uncontrolled medical conditions that the investigator feels might
             compromise study participation

          -  Major surgery within 4 weeks of the start of study treatment, without complete
             recovery

          -  Unwillingness to give written informed consent

          -  Unwillingness to participate or inability to comply with the protocol for the duration
             of the study

          -  Patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome
             (AIDS) and those severely immunocompromised will be excluded; however, no patients
             will be tested for HIV
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival(PFS)
Time Frame:Time from study day 1 to the time the patient is first recorded as having disease progression or death, assessed up to 2 years
Safety Issue:
Description:Continuous variables will be expressed by means, standard deviations and 95% confidence intervals. Estimated using the Kaplan-Meier estimator with confidence interval calculated based on the Brookmeyer-Crowley method.

Secondary Outcome Measures

Measure:Frequency and severity of toxicities of the regimens, graded according to the NCI CTCAE v4.0
Time Frame:Up to 2 years
Safety Issue:
Description:Frequencies will be computed for discrete data.
Measure:Overall response rate, as described in RECIST v1.1 criteria
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Time from study day 1 to the date of death or the last date the patient was known to be alive, assessed up to 1 year
Safety Issue:
Description:Continuous variables will be expressed by means, standard deviations and 95% confidence intervals. Kaplan-Meier estimator will be used.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:John Hays

Trial Keywords

  • Metastatic colon cancer

Last Updated

February 1, 2018