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

NCT ID: NCT00423696

Last Updated: 2021-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-23
• Study Completion Date: 2011-08-01

Brief Summary

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 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. It is not yet known which combination chemotherapy regimen is more effective when given together with bevacizumab in treating patients with colorectal cancer.

PURPOSE: This randomized phase II trial is studying bevacizumab to compare how well it works when given together with two different combination chemotherapy regimens as first-line therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

• Compare the progression-free survival at 6 months in patients with unresectable metastatic colorectal cancer treated with first-line therapy comprising bevacizumab and irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) vs bevacizumab and irinotecan hydrochloride and capecitabine (XELIRI).

Secondary

• Compare the toxicities of these regimens in these patients.
• Compare the objective response rate and duration of response in patients treated with these regimens.
• Compare the tumor control in patients treated with these regimens.
• Compare the progression-free and overall survival of patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center, WHO performance status (0 or 1 vs 2), age (< 65 years vs ≥ 65 years), and number of metastatic sites (1 vs ≥ 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive bevacizumab IV over 30-90 minutes, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive bevacizumab alone every 2 weeks in the absence of disease progression.
• Arm II: Patients receive bevacizumab IV over 30-90 minutes and irinotecan hydrochloride IV over 90 minutes on day 1 and oral capecitabine on days 1-14. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive bevacizumab alone every 3 weeks in the absence of disease progression.

Quality of life is assessed periodically.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 144 patients will be accrued for this study.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

bevacizumab + FOLFIRI

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

fluorouracil

Intervention Type: DRUG

irinotecan hydrochloride

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

bevacizumab + XELIRI

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

capecitabine

Intervention Type: DRUG

irinotecan hydrochloride

Intervention Type: DRUG

Interventions

bevacizumab

Intervention Type: BIOLOGICAL

capecitabine

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

irinotecan hydrochloride

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

• Unresectable metastatic disease
• Measurable disease
• No CNS metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Life expectancy > 3 months
• Absolute neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 9 g/dL (transfusion allowed)
• INR < 1.5
• Alkaline phosphatase < 1.5 times upper limit of normal (ULN)
• Bilirubin < 1.5 times ULN
• AST and ALT < 2.5 times ULN (5 times ULN if liver metastases are present)
• Creatinine clearance > 30 mL/min
• Urine protein < 2+ OR ≤ 1 g/L by 24-hour urine collection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No contraindications to study therapy
• No gastrointestinal or duodenal ulcers
• No AIDS
• No serious illness, active infection, or other serious condition that would preclude study therapy
• No coagulation problem
• No bleeding diathesis
• No sensitivity to Chinese hamster ovarian cells or other recombinant human antibodies
• No severe renal insufficiency
• No uncontrolled hypertension
• No active or severe cardiovascular conditions, including the following:

• Cerebrovascular accident
• Myocardial infarction within the past 6 months
• New York Heart Association class II-IV cardiac insufficiency
• Severe cardiac arrhythmia (even if treated)
• No primitive stenosis or symptomatic peritoneal carcinosis causing a risk of intestinal subocclusion or occlusion
• No nonhealing wound or fracture
• No prior thromboembolic disease
• No other cancer within the past 2 years except for basal cell skin cancer or carcinoma in situ of the uterine cervix
• No geographical, social, or psychological condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy for metastatic disease
• At least 6 months since prior adjuvant chemotherapy (fluorouracil with or without oxaliplatin)

• No prior adjuvant chemotherapy comprising irinotecan hydrochloride with or without bevacizumab
• At least 28 days since prior major surgery
• Prior radiotherapy allowed except to target lesions
• At least 10 days since prior anticoagulants
• No concurrent chronic acetylsalicylic acid (at doses > 325 mg/day)
• No other concurrent investigational therapy
• No other concurrent anticancer therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michel Ducreux, MD, PhD

Role: STUDY_CHAIR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

C.H.U. de Brest

Brest, , France

Centre Regional Francois Baclesse

Caen, , France

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, , France

Centre Oscar Lambret

Lille, , France

Polyclinique des Quatre Pavillons

Lormont, , France

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, , France

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, , France

Centre Antoine Lacassagne

Nice, , France

Institut Curie Hopital

Paris, , France

Polyclinique Francheville

Périgueux, , France

Institut Jean Godinot

Reims, , France

Centre Eugene Marquis

Rennes, , France

Centre Rene Huguenin

Saint-Cloud, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

References

Malka D, Boige V, Jacques N, Vimond N, Adenis A, Boucher E, Pierga JY, Conroy T, Chauffert B, Francois E, Guichard P, Galais MP, Cvitkovic F, Ducreux M, Farace F. Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab. Ann Oncol. 2012 Apr;23(4):919-27. doi: 10.1093/annonc/mdr365. Epub 2011 Aug 8.

Reference Type: RESULT

PMID: 21825101 (View on PubMed)

Antoun S, Bayar MA, Dyevre V, Lanoy E, Smolenschi C, Ducreux M. No evidence for changes in skeletal muscle mass or weight during first-line chemotherapy for metastatic colorectal cancer. BMC Cancer. 2019 Aug 28;19(1):847. doi: 10.1186/s12885-019-6086-2.

Reference Type: DERIVED

PMID: 31462288 (View on PubMed)

Other Identifiers

FRE-FNCLCC-ACCORD-13-0503

Identifier Type: OTHER

Identifier Source: secondary_id

EU-20666

Identifier Type: REGISTRY

Identifier Source: secondary_id

2005-000070-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDR0000523435

Identifier Type: -

Identifier Source: org_study_id