Clinical trial NCT00025337: Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated
Official title: Phase III Trial of Bevacizumab (NSC 704865), Oxaliplatin (NSC 266046), Fluorouracil and Leucovorin Versus Oxaliplatin, Fluorouracil and Leucovorin Versus Bevacizumab Alone in Previously Treated Patients With Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Adenocarcinoma of the Colon
Adenocarcinoma of the Rectum
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage III Colon Cancer
Stage III Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 880
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without bevacizumab in treating patients who have advanced or metastatic colorectal cancer that has been previously treated. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with combination chemotherapy may kill more tumor cells. It is not yet known if bevacizumab is more effective with or without combination chemotherapy in treating colorectal cancer

Detailed description: OBJECTIVES:

I. Compare the response, time to progression, and overall survival of patients with previously treated advanced or metastatic colorectal adenocarcinoma treated with oxaliplatin, leucovorin calcium, and fluorouracil with or without bevacizumab versus bevacizumab only. (Arm III closed to accrual as of 03/11/2003).

II. Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to ECOG performance status (0 vs 1 or 2), and prior radiotherapy (yes vs no). Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive bevacizumab IV over 30-90 minutes and oxaliplatin IV over 2 hours on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil (5-FU) IV over 22 hours on days 1 and 2.

Arm II: Patients receive oxaliplatin, leucovorin calcium, and 5-FU as in arm I.

Arm III: Patients receive bevacizumab as in arm I. (Arm closed to accrual as of 03/11/2003).

Courses in all arms repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response may receive 2 additional courses.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the colon or rectum

  * Advanced or metastatic disease
  * Must have received a fluoropyrimidine-based regimen and an irinotecan-based regimen, either alone or in combination, for advanced disease
  * May have relapsed within 6 months of adjuvant therapy with fluorouracil (5-FU) (or combination 5-FU and irinotecan) and progressed after single-agent irinotecan
* Measurable disease
* No known brain metastases
* Performance status - ECOG 0-2
* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* No history of thrombotic or hemorrhagic disorders
* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* AST no greater than 5 times ULN
* INR no greater than 1.5
* PTT no greater than ULN
* Creatinine no greater than 1.5 times ULN
* Proteinuria less than 1+ (i.e., 0 or trace)
* Protein less than 500 mg by 24-hour urine collection
* Proteinuria secondary to ureteral stents allowed

  * No proteinuria secondary to nephropathy
* Controlled hypertension (less than 150/100 mm Hg) allowed if on a stable antihypertensive regimen
* No prior myocardial infarction
* No uncontrolled congestive heart failure
* No unstable angina within the past 3 months
* No serious nonhealing wound, ulcer, or bone fracture
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No prior bevacizumab
* See Disease Characteristics
* Recovered from prior chemotherapy
* No prior oxaliplatin
* At least 2 weeks since prior radiotherapy and recovered
* At least 28 days since prior major surgical procedure
* At least 10 days since prior aspirin dose of more than 325 mg/day
* No concurrent therapeutic anticoagulation except prophylactic anticoagulation of venous access device
* No concurrent antiplatelet agents (e.g., dipyridamole, ticlopidine, clopidogrel, or cilostazol)
* No concurrent oral cryotherapy on day 1 of oxaliplatin administration

Primary outcomes:
measure: Overall survival
timeFrame: From the date of entry on study, assessed up to 5 years
Secondary outcomes:
measure: Response defined using RECIST criteria
timeFrame: Up to 5 years
measure: Progression free survival
timeFrame: From the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression, assessed up to 5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Eastern Cooperative Oncology Group
state: Massachusetts
Study officials:
affiliation: Eastern Cooperative Oncology Group
name: Bruce Giantonio
role: PRINCIPAL_INVESTIGATOR
References: