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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00423696
First received: January 16, 2007
Last updated: September 28, 2011
Last verified: September 2011
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Drug: capecitabine
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Randomized Study of First-Line Therapy Comprising Bevacizumab and Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil (FOLFIRI) Versus Bevacizumab and Irinotecan Hydrochloride and Capecitabine (XELIRI) in Patients With Unresectable Metastatic Colorectal Cancer [ACCORD]

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival at 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of objective responses [ Designated as safety issue: No ]
  • Percentage of stable disease responses [ Designated as safety issue: No ]
  • Duration of objective response and stable disease [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Toxicities [ Designated as safety issue: Yes ]
  • Quality of life [ Designated as safety issue: No ]

Estimated Enrollment: 144
Study Start Date: January 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00423696

Locations
France
C.H.U. de Brest
Brest, France, 29200
Centre Regional Francois Baclesse
Caen, France, 14076
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France, 21079
Centre Oscar Lambret
Lille, France, 59020
Polyclinique des Quatre Pavillons
Lormont, France, 33310
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
Marseille, France, 13273
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Montpellier, France, 34298
Centre Antoine Lacassagne
Nice, France, 06189
Institut Curie Hopital
Paris, France, 75248
Polyclinique Francheville
Perigueux, France, 24004
Institut Jean Godinot
Reims, France, 51056
Centre Eugene Marquis
Rennes, France, 35062
Centre Rene Huguenin
Saint Cloud, France, 92210
Centre Alexis Vautrin
Vandoeuvre-les-Nancy, France, 54511
Institut Gustave Roussy
Villejuif, France, F-94805
Sponsors and Collaborators
UNICANCER
Investigators
Study Chair: Michel Ducreux, MD, PhD Gustave Roussy, Cancer Campus, Grand Paris
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00423696     History of Changes
Other Study ID Numbers: CDR0000523435, FRE-FNCLCC-ACCORD-13-0503, EU-20666, EUDRACT-2005-000070-43
Study First Received: January 16, 2007
Last Updated: September 28, 2011
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Capecitabine
Irinotecan
Bevacizumab
Camptothecin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on July 23, 2014