A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer

Sponsor
Genentech, Inc.
Study ID
NCT00636610
Phase
PHASE2
Status
Completed

Conditions

  • Metastatic Colorectal Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Vismodegib 150 mg — DRUG
    Vismodegib 150 mg was provided in hard gelatin capsules in 3 different strengths, 25 mg, 125 mg, and 150 mg.
  • Placebo to vismodegib — DRUG
    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.
  • Bevacizumab — DRUG
    Bevacizumab 5 mg/kg was administered intravenously (IV) over 90 minutes for the first infusion, shortening to 60 and 30 minutes for subsequent infusions.
  • Modified FOLFOX — DRUG
    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.
  • FOLFIRI — DRUG
    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.

Study Details

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.

Key Dates

First listed
Mar 14, 2008
Start date
May 31, 2008
Status verified
May 2017
Primary completion
Dec 31, 2010
Completion
Dec 31, 2010

Study Design

Enrollment
199 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Vismodegib 150 mg
    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.
  • Placebo Comparator: Placebo to vismodegib
    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.

Primary Outcome Measure

Progression-free Survival (PFS) [ Time Frame: From first treatment through the data cut-off date of March 15, 2010, up to 90 weeks ]

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