Clinical trial NCT00418938
Conditions: Cancer Colon Cancer Colorectal Cancer Metastatic Cancer Rectal Cancer Metastatic Colorectal Cancer
Keywords: EGFR FOLFIRI 2nd Line Therapy 2nd Line mCRC Therapy mCRC Irinotecan panitumumab bevacizumab
Sponsor: Amgen
Start date: 2006-11-01; Completion date: 2013-04-01
Enrollment: 266 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multi-center, open-label, randomized, phase 2, two-arm clinical trial to be conducted in the United States. Approximately 210 eligible KRAS wild-type expressing metastatic colorectal cancer subjects who have failed first-line oxaliplatin-based chemotherapy (with at least 4 doses of oxaliplatin-based chemotherapy) with at least 4 doses of bevacizumab (failure is defined as toxicity due to oxaliplatin-based chemotherapy or progression of disease on first-line treatment) will be randomized in a 1:1 ratio to receive either a once-every-two-weeks (Q2W) FOLFIRI regimen plus panitumumab 6 mg/kg or a Q2W FOLFIRI regimen plus bevacizumab (either 5 mg/kg or 10 mg/kg, depending on physician choice and institutional standard of care).

Detailed description:
This phase 2, multicenter, open-label, randomized, two-arm study was designed to estimate the treatment effect of panitumumab in combination with FOLFIRI compared to bevacizumab in combination with FOLFIRI in subjects with metastatic colorectal cancer (mCRC) who had failed first-line therapy with at least 4 doses of oxaliplatin-based chemotherapy and bevacizumab. After data became available demonstrating that the treatment effect of antiepidermal growth factor receptor (EGFR) agents was limited to patients with wild-type Kirsten rat Sarcoma-2 virus (KRAS) mCRC, the study was amended to enroll only subjects with wild-type KRAS tumors. Eligible subjects were randomized in a 1:1 ratio to receive panitumumab 6 mg/kg plus FOLFIRI once every 2 weeks (Q2W) or bevacizumab 5 mg/kg or 10 mg/kg plus FOLFIRI Q2W. Randomization was stratified by the reason for first-line treatment failure (progression vs toxicity) and by intended bevacizumab dose (5 mg/kg vs 10 mg/kg). The intended bevacizumab doses were ascertained from sites at the time of site initiation. Subjects were treated with all or any components of second-line treatment until the occurrence of unacceptable adverse events, disease progression, death, loss to follow up, or study withdrawal by the subject, investigator, or sponsor. Tumor response was evaluated by blinded central radiology review per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 and by the investigator using either modified RECIST version 1.0 or clinical assessment. After subjects permanently discontinued all components of second-line treatment, they were to undergo a safety follow-up assessment 30 (± 7) days after the last dose. Subjects ending second-line treatment before disease progression were followed for PFS (radiographic disease assessment) every 12 weeks (± 14 days) from the safety follow-up visit until disease progression, initiation of a new therapy for mCRC, or until approximately 100 PFS events were observed in subjects with wild-type KRAS tumors. Subjects were also followed for survival every 12 weeks (± 14 days) from the safety follow-up assessment until approximately 100 PFS events were observed in subjects with wild-type KRAS tumors.

Arms: arm 1: FOLFIRI + Panitumumab arm 2: FOLFIRI + Bevacizumab
Interventions: intervention 1: Panitumumab intervention 2: Bevacizumab intervention 3: Leucovorin intervention 4: Irinotecan intervention 5: 5-Fluorouracil
Intervention descriptions: intervention 1: 6mg/kg IV intervention 2: Either 5mg/kg OR 10mg/kg IV intervention 3: 400mg/m\^2 IV (in the vein) intervention 4: 180mg/m\^2 IV (in the vein) intervention 5: 400mg/m\^2 bolus IV (in the vein) over 2-4 min, followed by 2400mg/m\^2 continuous IV over 46 hours for the first 2 cycles, increased to 3000mg/m\^2 thereafter if no significant side effects

Protocol documents: