- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00070122
Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
A Phase III Trial of Modified FOLFOX6 Versus CAPOX, With Bevacizumab (NSC-704865) or Placebo, as First-Line Therapy in Patients With Previously Untreated Advanced Colorectal Cancer
Study Overview
Status
Conditions
Detailed Description
OBJECTIVES:
I. Compare overall survival in patients with locally advanced, metastatic, or recurrent colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab vs capecitabine, oxaliplatin, and bevacizumab.
II. Compare progression-free survival and time to treatment failure in patients treated with these regimens.
III. Compare the response of patients with measurable disease treated with these regimens.
IV.Compare toxicity rates of these regimens in these patients. V. Compare patient-reported functional status and convenience of therapy in patients treated with these regimens.
VI. Correlate germline polymorphisms of DNA repair (e.g., ERCC-1, XRCC1, GST-P1, XPD, and ribonucleotide reductase), target enzymes (e.g., thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase), angiogenesis (e.g., vascular endothelial growth factor), and growth factors (e.g., epithelial growth factor receptor) with survival, progression-free survival, and toxicity from chemotherapy in patients treated with these regimens.
VII. Correlate tumor mRNA expression levels of similar DNA repair enzymes as well as enzymes involved in angiogenesis with survival and progression-free survival in patients treated with these regimens.Correlate tumor mRNA expression levels of similar target enzymes before treatment with survival, progression-free survival, and toxicity in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 or 1 vs 2) and prior adjuvant therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
ARM II: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine on days 1-15. Patients are further randomized to receive bevacizumab or placebo* as in arm I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
Patients are followed every 3 months until disease progression. After disease progression, patients are followed every 6 months for 2 years and then annually for up to 4 years after study entry.
PROJECTED ACCRUAL: A total of 2,200 patients (1,100 per treatment arm) will be accrued for this study within 3 years.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Texas
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San Antonio, Texas, United States, 78245
- Southwest Oncology Group
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologically or cytologically confirmed locally advanced, recurrent, or metastatic colorectal adenocarcinoma
- Not curable by surgery or amenable to radiotherapy with curative intent
Previously resected colorectal cancer with new evidence of metastasis does not require separate histologic or cytologic confirmation unless one of the following is true:
- More than 5 years has elapsed between primary surgery and development of metastatic disease
- Primary tumor was T1-T2, N0, M0
- Site of primary lesion must be or have been in the large bowel as determined by endoscopy, radiology, or surgery
- Measurable or evaluable disease
- No known brain or leptomeningeal disease
- Performance status - Zubrod 0-2
- No history of hemorrhagic or thrombotic disorders
- Absolute neutrophil count greater than 1,500/mm^3
- Platelet count greater than 100,000/mm^3
- Bilirubin no greater than 2.0 times upper limit of normal (ULN)
- SGOT no greater than 2.5 times ULN (5 times ULN for patients with liver involvement)
- Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN for patients with liver involvement or 10 times ULN for patients with bone involvement)
- INR no greater than 1.5
- PTT no greater than ULN
- Creatinine no greater than 1.5 times ULN
- Creatinine clearance at least 50 mL/min
- Proteinuria less than 1+*
- Protein less than 500mg/24 hours*
No uncontrolled hypertension
- Hypertension must be well-controlled (i.e., less than 160/90) and on a stable regimen of antihypertensive therapy
- No unstable angina
- No symptomatic congestive heart failure
- No myocardial infarction within the past 6 months
- No serious uncontrolled cardiac arrhythmia
- No New York Heart Association class III or IV heart disease
- No symptomatic pulmonary fibrosis
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
- No active or uncontrolled severe infection
No contraindication to oral medications (e.g., severe dysphagia)
- G-tubes or J-tubes allowed
- No peripheral neuropathy greater than grade 1
- No serious non-healing wound, ulcer, or bone fracture
- No significant traumatic injury within the past 28 days
- No other severe acute or chronic medical condition or laboratory abnormality that would preclude study participation
- No psychiatric condition that would preclude study participation
- No prior bevacizumab
- No prior oxaliplatin
No prior chemotherapy for advanced colorectal cancer
- Prior adjuvant therapy for resected stage II-III disease allowed provided at least 12 months have elapsed between completion of therapy and diagnosis of recurrent disease
- At least 28 days since prior radiotherapy and recovered
- See Disease Characteristics
- More than 28 days since prior major surgical procedure or open biopsy
- More than 7 days since prior fine needle aspiration or core biopsy
- No concurrent major surgery
- More than 10 days since prior full-dose aspirin (325 mg)
- No concurrent antiplatelet agents (e.g., dipyridamole, ticlopidine, clopidogrel, or cilostazol)
- No other concurrent investigational agents
No concurrent therapeutic anticoagulation
- Prophylactic anticoagulation of central venous lines allowed
- Low-dose prophylactic enoxaparin or heparin allowed
- No concurrent cimetidine
- No concurrent sorivudine or its related analogs (e.g., brivudine)
- No concurrent use of a cold cap or iced mouth rinses
Study Plan
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: Arm I (oxaliplatin, leucovorin calcium, fluorouracil)
Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1.
Patients are further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1.
Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
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Experimental: Arm II (oxaliplatin, capecitabine)
Patients receive oxaliplatin IV over 2 hours on day 1and oral capecitabine on days 1-15.
Patients are further randomized to receive bevacizumab or placebo* as in arm I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given orally
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival in patients with colorectal cancer treated with fluorouracil/leucovorin calcium and oxaliplatin with and without becavizumab versus those treated with capecitabine and oxaliplatin with our without bevacizumab
Time Frame: Up to 6 years
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Will be analyzed primarily by the stratified Cox model.
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Up to 6 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to treatment failure
Time Frame: Up to 6 years
|
Will be analyzed primarily by the Cox stratified model.
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Up to 6 years
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Progression-free survival
Time Frame: Up to 6 years
|
Will be analyzed primarily by the Cox stratified model.
|
Up to 6 years
|
Response (among patients with measurable disease)
Time Frame: Up to 6 years
|
Will be analyzed primarily by the Cox stratified model.
|
Up to 6 years
|
Treatment toxicities graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 3.0)
Time Frame: Up to the time of progression
|
Up to the time of progression
|
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Change in FACT-C TOI
Time Frame: Baseline to 25 weeks
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The analysis for evaluating this change will be a comparison of the change score between the first and last assessment.
If cohort patterns for mean scores do not show signs of informative missing data, a mixed effects linear model approach will be used to measure change in FACT-C TOI scores.
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Baseline to 25 weeks
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Change in Chemotherapy Convenience and Satisfaction Questionnaire scores
Time Frame: Baseline to 25 weeks
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Effect size will be used to compare the size of the difference in each arm.
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Baseline to 25 weeks
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Whether gene expression variables are predictive of survival and progression-free survival
Time Frame: Up to 6 years
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Up to 6 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Charles Blanke, Southwest Oncology Group
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Recurrence
- Adenocarcinoma
- Rectal Neoplasms
- Colonic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Micronutrients
- Vitamins
- Antidotes
- Vitamin B Complex
- Antibodies
- Fluorouracil
- Capecitabine
- Oxaliplatin
- Immunoglobulins
- Bevacizumab
- Leucovorin
- Levoleucovorin
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
Other Study ID Numbers
- NCI-2012-02556
- U10CA032102 (U.S. NIH Grant/Contract)
- S0303
- CDR0000330000 (Registry Identifier: PDQ (Physician Data Query))
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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