- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00636610
A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer
May 15, 2017 updated by: Genentech, Inc.
A Randomized, Placebo-Controlled Phase II Study of Vismodegib (GDC-0449, Systemic Hedgehog Antagonist) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
199
Phase
- Phase 2
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age ≥ 18 years
- Histologically confirmed metastatic colorectal cancer (CRC)
- Representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report, must be confirmed to be available and requested at any time prior to entry of study
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate hematopoetic capacity
- Adequate hepatic function
- Adequate renal function
- Use of an effective method of barrier contraception (for women of childbearing potential)
- Signed informed consent
Exclusion Criteria:
- Prior chemotherapy for metastatic CRC or adjuvant chemotherapy for CRC within the prior 6 months
- Clinically suspected or confirmed CNS metastases or carcinomatous meningitis
- Major surgical procedure within 4 weeks prior to the first day of treatment in this study (Day 1)
- Pelvic radiation within 2 weeks prior to Day 1
- Wound dehiscence requiring intervention, gastrointestinal perforation, or bowel obstruction
- Pregnancy or lactation
- Uncontrolled medical illnesses including the following: Infection requiring intravenous (IV) antibiotics, congestive heart failure not controlled with medication, hypertension not controlled with medication
- Thromboembolic disease
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Vismodegib 150 mg was provided in hard gelatin capsules in 3 different strengths, 25 mg, 125 mg, and 150 mg.
Other Names:
Bevacizumab 5 mg/kg was administered intravenously (IV) over 90 minutes for the first infusion, shortening to 60 and 30 minutes for subsequent infusions.
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.
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.
|
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.
|
Bevacizumab 5 mg/kg was administered intravenously (IV) over 90 minutes for the first infusion, shortening to 60 and 30 minutes for subsequent infusions.
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.
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS)
Time Frame: From first treatment through the data cut-off date of March 15, 2010, up to 90 weeks
|
Progression-free survival (PFS) was defined as the time from randomization to the earlier of documented disease progression (PD) or death from any cause.
PD: At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
For patients without measurable disease, PD was defined as an increase in the size of a lesion to one that is measurable or unequivocal progression of a non-target lesion.
|
From first treatment through the data cut-off date of March 15, 2010, up to 90 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS) in Patients With Various Degrees of Hedgehog Antigen Tumor Expression
Time Frame: From first treatment through the data cut-off date of March 15, 2010, up to 90 weeks
|
Indian + Sonic Hedgehog antigen expression was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) from archival tumor tissue taken from each patient prior to enrollment in the study.
Results are reported in 3 categories; the 33% of patients with the lowest level of expression, the 35% of patients with a middle level of expression, and the 32% of patients with the highest level of expression.
PFS was defined as the time between randomization and disease progression, as confirmed by radiography, or death for any reason.
|
From first treatment through the data cut-off date of March 15, 2010, up to 90 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Jennifer Low, M.D., Ph.D., Genentech, Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 1, 2008
Primary Completion (Actual)
December 1, 2010
Study Completion (Actual)
December 1, 2010
Study Registration Dates
First Submitted
March 5, 2008
First Submitted That Met QC Criteria
March 11, 2008
First Posted (Estimate)
March 14, 2008
Study Record Updates
Last Update Posted (Actual)
June 8, 2017
Last Update Submitted That Met QC Criteria
May 15, 2017
Last Verified
May 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
Other Study ID Numbers
- SHH4429g
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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