Comparison of Treatment Effect of Chemotherapy With Panitumumab to Chemotherapy Alone

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the treatment effect of panitumumab plus FOLFIRI compared to FOLFIRI alone as second line therapy for metastatic colorectal cancer.

Official Title
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A Randomized, Multicenter Phase 3 Study to Compare the Efficacy of Panitumumab in Combination With Chemotherapy to the Efficacy of Chemotherapy Alone in Patients With Previously Treated Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Panitumumab
* Drug: FOLFIRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man or woman at least 18 years old Diagnosis of metastatic colorectal cancer (mCRC) One and only one chemotherapy regimen for mCRC consisting of first-line 5-FU -based chemotherapy Radiologically documented disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria during treatment or within 6 months of last dose of first-line chemotherapy At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2 Paraffin-embedded tumor tissue from the primary tumor or metastasis available for central analyses Adequate hematologic, renal, and hepatic functions Negative pregnancy test within 72 hours of enrollment Other protocol-specified criteria may apply Exclusion Criteria: History of or known presence of central nervous system (CNS) metastases History of another primary cancer within 5 years of randomization Prior irinotecan therapy Prior anti-epidermal growth factor receptor (EGFr) antibody therapy or treatment with small molecule EGFr inhibitors Any investigational agent or therapy within 30 days before randomization Known allergy or hypersensitivity to irinotecan, 5-FU or leucovorin History of interstitial lung disease or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan Active inflammatory bowel disease or other bowel disease causing chronic diarrhea Known positive tests for human immunodefiency virus (HIV), hepatitis C viris (HCV), acute or chronic active hepatitis B virus (HBV) Major surgery within 28 days of randomization or minor surgical procedure within 14 days of randomization Pregnant or breast-feeding Man or woman of child-bearing potential not consenting to use adequate contraceptive methods or abstinence during the course of the study and for 6 months after last study drug administration (women) or 1 month after last study drug administration (men) Other protocol-specified criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panitumumab Plus FOLFIRI<br>Participants received panitumumab as an intravenous (IV) infusion at a dose of 6 mg/kg plus a standard chemotherapy regimen (FOLFIRI) consisting of 5-fluorouracil (5-FU), leucovorin and irinotecan. Treatment was administered in cycles every two weeks. | Drug: Panitumumab<br>* Panitumumab was administered by IV infusion on Day 1 of each 14-day cycle, just before administration of FOLFIRI chemotherapy.<br>* Other names: Vectibix®;Drug: FOLFIRI<br>* FOLFIRI chemotherapy was initiated on Day 1 of each treatment cycle at the following starting doses: irinotecan 180 mg/m^2, leucovorin 400 mg/m^2 racemate (or 200 mg/m^2 I-leucovorin), 5-FU bolus 400 mg/m^2, 5-FU infusion 2400 mg/m^2.<br>|
| Active Comparator: FOLFIRI Alone<br>Participants received standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment is administered in cycles every two weeks. | Drug: FOLFIRI<br>* FOLFIRI chemotherapy was initiated on Day 1 of each treatment cycle at the following starting doses: irinotecan 180 mg/m^2, leucovorin 400 mg/m^2 racemate (or 200 mg/m^2 I-leucovorin), 5-FU bolus 400 mg/m^2, 5-FU infusion 2400 mg/m^2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Progression-free survival was defined as the time from randomization to first disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria or death, based on independent central radiological assessment. Participants who were alive but did not meet criteria for progression by the data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions. | From randomization until the data cut-off date of 8 April 2008. Maximum follow-up time was 17 months. | 
| Overall Survival | Overall survival was defined as the time from randomization to the date of death. Participants who had not died by the analysis data cutoff date had their time of death censored at their last contact date. | From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Objective Response | Participants were evaluated for tumor response per the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 8 weeks until disease progression. Objective response was defined as the incidence of either a confirmed complete or partial response (CR or PR) while on study, as determined by blinded independent central review and confirmed no less than 4-weeks after the criteria for response are first met. CR: Disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions and no progression of non-target or no new lesions, or, disappearance of all target lesions and the persistence of ≥ 1 non-target lesion not qualifying for either CR or progressive disease. Participants without a post-baseline assessment were considered non-responders. | Every 8 weeks until disease progression up to the data cut-off date of 30 April 2009. Maximum time on follow-up was 33 months. | 
| Time to Disease Progression | Time to progression was defined as the time from the randomization date to the date of first observed disease progression per the modified RECIST criteria. Participants not meeting these criteria by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions. | From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months | 
| Duration of Response | Calculated only for those participants with an objective response as the time from the first objective response (subsequently confirmed within no less than 4 weeks) to first observed disease progression per modified-RECIST criteria. Participants not meeting these criteria by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions. | From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months | 
| Number of Participants With Adverse Events (AEs) | A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the subject at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The relationship of the adverse event to the study treatment was assessed by the Investigator by means of the question: Is there a reasonable possibility that the event may have been caused by the study treatment? | From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncology, Cancer, Metastatic Colorectal Cancer, EGFr, Panitumumab, Clinical Trial, Amgen