Clinical trial NCT00416494: Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer
Official title: Phase II Study of Oxaliplatin, Capecitabine and Bevacizumab in the Treatment of Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the colon
recurrent colon cancer
stage IV colon cancer
adenocarcinoma of the rectum
recurrent rectal cancer
stage IV rectal cancer
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-12-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 criteria: 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

Primary outcomes:
measure: Response Rate (Percentage of Participants With Partial or Complete Response)
timeFrame: After all subjects were evaluated for restaging which occured every 9 weeks from drug initiation until disease progression, assesed up to 24 months.
Secondary outcomes:
measure: Time to Progression
timeFrame: From time of treatment until documented progression, assesed up to 60 months.
measure: Disease Free Survival
timeFrame: From time of treatment until documented progression or death from any cause, whichever came first, assesed up to 60 months.
measure: Overall Survival
timeFrame: From time of treatment until death from any cause, assesed up to 60 months.
measure: Safety and Tolerability
timeFrame: After all participants went off study drug regimine.
Other outcomes:
measure: Effect on Angiogenesis Biomarkers
timeFrame: After study completion
measure: Effect on Wound Angiogenesis
timeFrame: After study completion
Locations:
Study officials:
affiliation: Duke Cancer Institute
name: Herbert I. Hurwitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Liu Y, Starr MD, Bulusu A, Pang H, Wong NS, Honeycutt W, Amara A, Hurwitz HI, Nixon AB. Correlation of angiogenic biomarker signatures with clinical outcomes in metastatic colorectal cancer patients receiving capecitabine, oxaliplatin, and bevacizumab. Cancer Med. 2013 Apr;2(2):234-42. doi: 10.1002/cam4.71. Epub 2013 Mar 6.