Clinical trial NCT00636610
Conditions: Metastatic Colorectal Cancer
Keywords: Hedgehog CRC Colorectal Cancer Hedgehog Pathway Inhibitor
Sponsor: Genentech, Inc.
Start date: 2008-05-01; Completion date: 2010-12-01
Enrollment: 199 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This was a randomized, placebo-controlled, double-blind study of vismodegib (GDC-0449) added to biochemotherapy standard-of-care regimens for metastatic colorectal cancer (CRC), with treatment until disease progression. Patients received either FOLFOX (FOL=leucovorin calcium \[folinic acid\], F=fluorouracil, OX=oxaliplatin) or FOLFIRI (FOL=leucovorin calcium \[folinic acid\] F=fluorouracil, IRI=irinotecan hydrochloride) chemotherapy with bevacizumab. The decision of which regimen (FOLFOX or FOLFIRI) to use was made by the treating physician and patient. Patients were randomized to receive vismodegib or placebo and were stratified based on the chemotherapy regimen chosen and whether or not Response Evaluation Criteria in Solid Tumors (RECIST) measurable disease was present at baseline.

Detailed description:

Arms: arm 1: Patients received vismodegib 150 mg orally once daily starting on Day 3 of each 2-week treatment cycle. In addition, patients received either Modified FOLFOX (FOL=leucovorin calcium \[folinic acid\], F=fluorouracil, OX=oxaliplatin) + bevacizumab or FOLFIRI (FOL=leucovorin calcium \[folinic acid\] F=fluorouracil, IRI=irinotecan hydrochloride) + bevacizumab on Days 1-3 of each 2-week treatment cycle. The decision of which regimen (FOLFOX or FOLFIRI) to use was made by the treating physician and patient. arm 2: Patients received placebo to vismodegib orally once daily starting on Day 3 of each 2-week treatment. In addition, patients received either Modified FOLFOX (FOL=leucovorin calcium \[folinic acid\], F=fluorouracil, OX=oxaliplatin) + bevacizumab or FOLFIRI (FOL=leucovorin calcium \[folinic acid\] F=fluorouracil, IRI=irinotecan hydrochloride) + bevacizumab on Days 1-3 of each 2-week treatment cycle. The decision of which regimen (FOLFOX or FOLFIRI) to use was made by the treating physician and patient.
Interventions: intervention 1: Vismodegib 150 mg intervention 2: Placebo to vismodegib intervention 3: Bevacizumab intervention 4: Modified FOLFOX intervention 5: FOLFIRI
Intervention descriptions: intervention 1: Vismodegib 150 mg was provided in hard gelatin capsules in 3 different strengths, 25 mg, 125 mg, and 150 mg. intervention 2: Placebo to vismodegib consisted of the excipients for vismodegib without the active molecule in hard gelatin capsules matching the active drug product in color and size. intervention 3: Bevacizumab 5 mg/kg was administered intravenously (IV) over 90 minutes for the first infusion, shortening to 60 and 30 minutes for subsequent infusions. intervention 4: Following administration of bevacizumab, patients received oxaliplatin 85 mg/m\^2 IV administered over 90 minutes concurrently with folinic acid 400 mg/m\^2 (d,I-racemic form, or 200 mg/m\^2 I-isomer form) IV administered over 120 minutes, then fluorouracil 400 mg/m\^2 administered as an IV bolus, then 2400 mg/m\^2 administered as a continuous IV infusion over 46 hours. intervention 5: Following administration of bevacizumab, patients received irinotecan 180 mg/m\^2 IV administered over 90 minutes concurrently with folinic acid 400 mg/m\^2 (d,I-racemic form, or 200 mg/m\^2 I-isomer form) administered IV over 120 minutes, then fluorouracil 400 mg/m\^2 administered as an IV bolus, then fluorouracil 2400 mg/m\^2 administered as a continuous IV infusion over 46 hours.

Protocol documents: