Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery (OMEGA)

Institut Bergonié

Status and phase: Completed; Phase 2

Conditions: Colorectal Cancer

Treatments: Genetic: polymorphism analysis; Biological: bevacizumab; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium

Study type: Interventional

Funder types: Other

Identifiers

NCT00467142

EUDRACT-2006-003901-22

IB-2006-31

IB-OMEGA

INCA-RECF0387

CDR0000540522

Details and patient eligibility

About

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with combination chemotherapy works as first-line therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.

Full description

OBJECTIVES:

Primary

• Determine the efficacy of bevacizumab, irinotecan hydrochloride, leucovorin calcium, and fluorouracil, in terms of partial or complete response, in patients with unresectable metastatic colorectal cancer.

Secondary

• Determine the duration of response in patients treated with this regimen.
• Determine the overall survival and progression-free survival of patients treated with this regimen.
• Determine the tolerability of this regimen in these patients.
• Assess the pharmacogenetics and change in genetic polymorphisms susceptible to modification by this regimen.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples are collected periodically for pharmacogenetic and genetic polymorphism analysis.

PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.

Enrollment: 62 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum

  • No other histological types

• Metastatic, unresectable disease

  • No bone metastases only

• Unidimensionally measurable metastatic disease

• No CNS metastases

PATIENT CHARACTERISTICS:

• WHO performance status (PS) 0-2 OR Karnofsky PS 70-100%

• Life expectancy ≥ 12 weeks

• ANC > 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 10 g/dL

• Bilirubin ≤ 1.25 times normal (1.5 times normal in presence of hepatic metastases)

• AST and ALT < 3 times normal (5 times normal in presence of hepatic metastases)

• Creatinine < 1.25 times normal

• No proteinuria

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other cancer in the past 5 years except for carcinoma in situ of the uterine cervix or basal cell skin cancer

• No hypersensitivity to fluorouracil

• No hypersensitivity to leucovorin calcium, bevacizumab, or their excipients

• No hypersensitivity to Chinese hamster ovarian cell products or other recombinant humanized or nonhumanized monoclonal antibodies

• No allergy to irinotecan hydrochloride

• No prior reaction to attenuated vaccines (fever, jaundice)

• No poor nutritional status

• No Biermer anemia or other anemia due to vitamin B12 deficiency

• No uncontrolled symptomatic occlusion or subocclusion

• No medullary hypoplasia or severe insufficiency

• No prior chronic intestinal disease

• No Gilbert's syndrome

• No intra-abdominal inflammatory reaction (e.g., gastroduodenal ulcer, diverticulitis, or colitis)

• No chronic intestinal inflammatory disease

• No thromboembolic arterial condition in the past 6 months, including any of the following:

  • Cardiovascular accident
  • Transient ischemic attack
  • Myocardial infarction

• No infection or serious noncancerous disease

• No condition that is unstable or would increase risk to the patient, including any of the following:

  • Unstable angina
  • Poorly controlled hypertension
  • Severe cardiac insufficiency
  • Serious arrhythmia
  • Bleeding diathesis
  • Pulmonary disease at risk of decompensation

• No familial, geographical, social, or psychological condition that would preclude study participation

• No prisoners or patients without guardians

PRIOR CONCURRENT THERAPY:

• At least 8 weeks since prior surgery
• At least 6 months since prior adjuvant chemotherapy
• At least 1 month since prior palliative chemotherapy
• No prior abdominal or pelvic radiotherapy
• At least 30 days since prior participation in another investigational study
• No prior bevacizumab
• No extensive intestinal resection (e.g., partial colectomy or extensive thin resection)
• No concurrent warfarin, Hypericum perforatum (St. John's wort), or prophylactic phenytoin

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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62 participants in 1 patient group

Folfiri and Bevacizumab

Experimental group

Description:

* Premedication = Dexchlorpheniramine, 5 mg in slow Direct IntraVeinous (DIV) on D1. * FOLFIRI (simplified LV5FU2 + irinotecan): * Irinotecan (Campto®): 180 mg/m² on D1 by IV infusion in 250 mL of 0.9% saline over 90 minutes. * LV5FU2, in its so-called "simplified" version, will be administered as follows L-folinic acid, as a 2-hour intravenous infusion, at a dose of 200 mg/m², on Day 1, in 500 mL of 5% glucose solution, concomitantly with the irinotecan infusion via a Y-tube, followed by 5 Fluorouracil (5 FU), intravenous bolus, at a dose of 400 mg/m² on D1, followed by 5 Fluorouracil (5 FU) as a 46-hour continuous infusion at a dose of 2400 mg/m² from D1 to D3, either in 1000 mL of 5% glucose solution, or in an electric syringe or pump dispenser * Bevacizumab (Avastin®): 5 mg/kg IV infusion in 100 mL of 0.9% saline over 90 minutes for the first infusion, then 60 minutes for the second infusion if tolerated, and 30 minutes for subsequent infusions if tolerated.

Treatment:

Drug: irinotecan hydrochloride

Drug: leucovorin calcium

Genetic: polymorphism analysis

Drug: fluorouracil

Biological: bevacizumab