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.
Overview
- Phase
- Phase 2
- Intervention
- panitumumab
- Conditions
- Mucinous Adenocarcinoma of the Colon
- Sponsor
- John Hays
- Enrollment
- 16
- Locations
- 2
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
John Hays
Principal Investigator
Ohio State University Comprehensive Cancer Center
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
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
Arms & Interventions
Treatment (panitumumab, combination chemotherapy)
5-Fluorouracil, irinotecan, and panitumumab
Intervention: panitumumab
Treatment (panitumumab, combination chemotherapy)
5-Fluorouracil, irinotecan, and panitumumab
Intervention: irinotecan hydrochloride
Treatment (panitumumab, combination chemotherapy)
5-Fluorouracil, irinotecan, and panitumumab
Intervention: fluorouracil
Treatment (panitumumab, combination chemotherapy)
5-Fluorouracil, irinotecan, and panitumumab
Intervention: leucovorin calcium
Outcomes
Primary Outcomes
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 3 years
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 Outcomes
- Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0(Up to 3 years)
- Proportion of Participants With Overall Response Rate, as Described in RECIST v1.1 Criteria(Up to 3 years)
- Overall Survival(Time from study day 1 to the date of death or the last date the patient was known to be alive, assessed up to 3 years)