Metastatic Colorectal CancerPhase 2NCT00636610
A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer
A Phase 2 study testing Vismodegib 150 mg, Bevacizumab and Modified FOLFOX in people with Metastatic Colorectal Cancer, run by Genentech, Inc..
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Vismodegib 150 mg, Bevacizumab and Modified FOLFOX
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 199 participants
- Where
- No sites listed yet
- Study dates
- May 2008to Dec 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Adequate renal function
- Use of an effective method of barrier contraception (for women of childbearing potential)
- Signed informed consent
Who cannot join
- 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
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- 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
About this study
Official title: 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.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Vismodegib 150 mg, Placebo to vismodegib, Bevacizumab, Modified FOLFOX, FOLFIRI
- Keywords
- Hedgehog, CRC, Colorectal Cancer, Hedgehog Pathway Inhibitor
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vismodegib 150 mgDrug
Also called GDC-0449, Erivedge
Vismodegib 150 mg was provided in hard gelatin capsules in 3 different strengths, 25 mg, 125 mg, and 150 mg.
Placebo to vismodegibDrug
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.
BevacizumabDrug
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 FOLFOXDrug
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.
FOLFIRIDrug
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 group | Role | What they receive |
|---|---|---|
| Vismodegib 150 mg | Experimental | 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. Receives: Drug: Vismodegib 150 mg; Drug: Bevacizumab; Drug: Modified FOLFOX; Drug: FOLFIRI |
| Placebo to vismodegib | Placebo comparator | 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. Receives: Drug: Placebo to vismodegib; Drug: Bevacizumab; Drug: Modified FOLFOX; Drug: FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
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.
Measured: From first treatment through the data cut-off date of March 15, 2010, up to 90 weeks
Secondary outcomes (1)
Progression-free Survival (PFS) in Patients With Various Degrees of Hedgehog Antigen Tumor Expression
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.
Measured: From first treatment through the data cut-off date of March 15, 2010, up to 90 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2008 (estimated)
- Study startMay 2008
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 199 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jennifer Low, M.D., Ph.D., Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00636610
- Sponsor's protocol ID
- SHH4429g
- Status last verified
- May 2017
- First submitted
- 5 Mar 2008
- Last updated
- 8 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00636610
- Acronym / sponsor ID
- SHH4429g
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Hedgehog, CRC, Colorectal Cancer, Hedgehog Pathway Inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 199 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2008 (actual)
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 14 Mar 2008 (estimated)
- Results
- Posted 3 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vismodegib 150 mg | Experimental | Drug: Vismodegib 150 mg, Drug: Bevacizumab, Drug: Modified FOLFOX, Drug: FOLFIRIPatients 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 to vismodegib | Placebo comparator | Drug: Placebo to vismodegib, Drug: Bevacizumab, Drug: Modified FOLFOX, Drug: FOLFIRIPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vismodegib 150 mgAlso: GDC-0449, ErivedgeVismodegib 150 mg was provided in hard gelatin capsules in 3 different strengths, 25 mg, 125 mg, and 150 mg. | Drug | Vismodegib 150 mg |
| Placebo to vismodegibPlacebo 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. | Drug | Placebo to vismodegib |
| BevacizumabBevacizumab 5 mg/kg was administered intravenously (IV) over 90 minutes for the first infusion, shortening to 60 and 30 minutes for subsequent infusions. | Drug | Placebo to vismodegib, Vismodegib 150 mg |
| Modified FOLFOXFollowing 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. | Drug | Placebo to vismodegib, Vismodegib 150 mg |
| FOLFIRIFollowing 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. | Drug | Placebo to vismodegib, Vismodegib 150 mg |
Primary outcome
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.
1 secondary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Low, M.D., Ph.D. study director
Genentech, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vismodegib 150 mg, Bevacizumab and Modified FOLFOX in people with Metastatic Colorectal Cancer, run by Genentech, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2017.