Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer
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Purpose
RATIONALE: Drugs used in chemotherapy, such as capecitabine, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving capecitabine and oxaliplatin together with bevacizumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with bevacizumab works in treating patients with metastatic or recurrent colorectal cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Colorectal Cancer |
Biological: bevacizumab Drug: oxaliplatin Drug: Capecitabine |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase II Study of Oxaliplatin, Capecitabine and Bevacizumab in the Treatment of Metastatic Colorectal Cancer |
- Response Rate (Percentage of Participants With Partial or Complete Response) [ Time Frame: After all subjects were evaluated for restaging which occured every 9 weeks from drug initiation until disease progression, assesed up to 24 months. ] [ Designated as safety issue: No ]
Restaging scans occurred every 9 weeks from time of study drug initiation until disease progression.
Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines.
The definitions were:
Complete response (CR)- Disappearance of all target lesions Partial response (PD)- At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Stable disease (SD)- Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
- Time to Progression [ Time Frame: From time of treatment until documented progression, assesed up to 60 months. ] [ Designated as safety issue: No ]
Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines.
Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
- Disease Free Survival [ Time Frame: From time of treatment until documented progression or death from any cause, whichever came first, assesed up to 60 months. ] [ Designated as safety issue: No ]
Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines.
Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
- Overall Survival [ Time Frame: From time of treatment until death from any cause, assesed up to 60 months. ] [ Designated as safety issue: No ]Average months of survival of participants after receiving study drug.
- Safety and Tolerability [ Time Frame: After all participants went off study drug regimine. ] [ Designated as safety issue: Yes ]Number of participants with adverse events
- Effect on Angiogenesis Biomarkers [ Time Frame: After study completion ] [ Designated as safety issue: No ]
- Effect on Wound Angiogenesis [ Time Frame: After study completion ] [ Designated as safety issue: No ]
| Enrollment: | 50 |
| Study Start Date: | September 2003 |
| Estimated Study Completion Date: | January 2016 |
| Primary Completion Date: | January 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Initial Cohort |
Biological: bevacizumab
10 mg/kg intravenously over 30-90 minutes on day 1
Drug: oxaliplatin
85 mg/m2 intravenously over 2 hours on day 1.
Drug: Capecitabine
Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort
|
| Experimental: Second cohort |
Biological: bevacizumab
10 mg/kg intravenously over 30-90 minutes on day 1
Drug: oxaliplatin
85 mg/m2 intravenously over 2 hours on day 1.
Drug: Capecitabine
Oral administration every 12 hours on days 1-5 and 8-12 850 mg/m2 in second cohort
|
Detailed Description:
OBJECTIVES:
Primary
- Evaluate the response rate in patients with previously untreated metastatic colorectal cancer treated with capecitabine, oxaliplatin, and bevacizumab.
Secondary
- Assess time to progression (TTP), disease-free survival (DFS), and overall survival (OS) in patients treated with this regimen.
- Assess the safety and tolerability of bevacizumab, oxaliplatin, and capecitabine in patients with previously untreated metastatic colorectal cancer.
Exploratory
- Evaluate the effect of this regimen on the biomarkers of angiogenesis.
- Assess the effect of this regimen on wound angiogenesis.
OUTLINE: Patients receive oral capecitabine twice daily on days 1-5 and 8-12, oxaliplatin IV over 2 hours on day 1, and bevacizumab IV over 1-1½ hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically documented adenocarcinoma of the colon or rectum
- Metastatic or recurrent disease not amenable to potentially curative treatment (e.g., inoperable metastatic disease)
- No leptomeningeal or brain metastases
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 2,000/mm^3
- Platelet count ≥ 100,000/mm^3
- AST/ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if known liver metastases)
- Bilirubin < 1.5 times ULN
- Creatinine clearance > 50 mL/min
No unstable or poorly controlled hypertension (> 150/100 mm Hg)
- Patients who have recently started or adjusted antihypertensive medications are eligible provided blood pressure is < 140/90 mm Hg on any new regimen for at least 3 different observations over 14 days
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during study and for at least 3-4 months after study completion
- No arterial or venous thrombosis (including cerebrovascular accident) within the last 3 months
- No known, existing, uncontrolled coagulopathy
- No clinically significant cardiac disease
- No congestive heart failure
- No symptomatic coronary artery disease
- No cardiac arrhythmias not well controlled with medication
- No myocardial infarction within the last 12 months
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin, capecitabine, or bevacizumab
- No history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior sorivudine or brivudine
- At least 6 months since prior adjuvant treatment with fluorouracil and leucovorin calcium or a fluorouracil and leucovorin calcium-based regimen
- No major surgery within 4 weeks without complete recovery
- No prior chemotherapy for metastatic/recurrent disease
- No cancer immunotherapy or other biologic therapy while on therapy
- No radiotherapy while on study
- No hormonal therapy for cancer while on study
- No full-dose warfarin (INR of > 1.5), heparin (> 10,000 units/day), or thrombolytic agents
- Allopurinol and cimetidine should be discontinued prior to starting on this regimen
Contacts and Locations More Information
Additional Information:
Publications:
| Responsible Party: | Herbert Hurwitz, Associate Professor of Medicine, Duke University Medical Center |
| ClinicalTrials.gov Identifier: | NCT00416494 History of Changes |
| Other Study ID Numbers: | Pro00008646, DUMC-4951-05-7R2, GENENTECH-DUMC-4951-05-7R2, SANOFI-DUMC-4951-05-7R2, ROCHE-DUMC-4951-05-7R2, CDR0000449971 |
| Study First Received: | December 27, 2006 |
| Results First Received: | February 12, 2013 |
| Last Updated: | March 25, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Duke University:
|
adenocarcinoma of the colon recurrent colon cancer stage IV colon cancer |
adenocarcinoma of the rectum recurrent rectal cancer stage IV rectal cancer |
Additional relevant MeSH terms:
|
Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Oxaliplatin Capecitabine Bevacizumab |
Fluorouracil Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013