Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

Phase II Study of Oxaliplatin, Capecitabine and Bevacizumab in the Treatment of Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00416494
• Other study ID #: Pro00008646
• Secondary ID: DUMC-4951-05-7R2
• Status: Completed
• Phase: Phase 2
• First received: December 27, 2006
• Last updated: August 25, 2014
• Start date: September 2003
• Est. completion date: August 2014

Study information

• Verified date: August 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: August 2014
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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.
• Capecitabine
Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort
• Capecitabine
Oral administration every 12 hours on days 1-5 and 8-12 850 mg/m2 in second cohort

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Herbert Hurwitz, MD	National Cancer Institute (NCI)

References & Publications (1)

Hurwitz H, Fernando N, Yu D, et al.: A phase II study of oxaliplatin, capecitabine and bevacizumab in the treatment of metastatic colorectal cancer. [Abstract] Ann Oncol 16 (Suppl 2): A-55P, ii285, 2005.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effect on Angiogenesis Biomarkers		After study completion	No
Other	Effect on Wound Angiogenesis		After study completion	No
Primary	Response Rate (Percentage of Participants With Partial or Complete Response)	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	After all subjects were evaluated for restaging which occured every 9 weeks from drug initiation until disease progression, assesed up to 24 months.	No
Secondary	Time to Progression	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.	From time of treatment until documented progression, assesed up to 60 months.	No
Secondary	Disease Free Survival	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.	From time of treatment until documented progression or death from any cause, whichever came first, assesed up to 60 months.	No
Secondary	Overall Survival	Average months of survival of participants after receiving study drug.	From time of treatment until death from any cause, assesed up to 60 months.	No
Secondary	Safety and Tolerability	Number of participants with adverse events	After all participants went off study drug regimine.	Yes