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Combination Chemotherapy and Bevacizumab With or Without Bevacizumab Maintenance Therapy in Treating Patients With Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00952029
Recruitment Status : Completed
First Posted : August 4, 2009
Last Update Posted : June 13, 2018
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive

Tracking Information
First Submitted Date  ICMJE August 1, 2009
First Posted Date  ICMJE August 4, 2009
Last Update Posted Date June 13, 2018
Study Start Date  ICMJE March 2010
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2013)
Disease-control duration [ Time Frame: one year after last patient included ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 1, 2009)
Objective response rate at 8 months according to RECIST criteria or MRI scan
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2013)
  • Objective response rate [ Time Frame: one year after last patient is included ]
  • Rate of non-hematologic grade 3-4 toxicities (except alopecia) [ Time Frame: one year after last patient is included ]
  • Overall toxicity rate [ Time Frame: one year after last patient is included ]
  • Duration of chemotherapy-free interval [ Time Frame: one year after last patient is included ]
  • Progression-free survival [ Time Frame: one year after last patient is included ]
  • Overall survival [ Time Frame: one and 2 year after last patient is included ]
  • Time-to-treatment failure [ Time Frame: one year after last patient is included ]
  • Quality of life as assessed by EORTC QLQ-C30 [ Time Frame: one year after last patient is included ]
  • Geriatric evaluation [ Time Frame: one year after last patient is included ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2009)
  • Rate of non-hematologic grade 3-4 toxicities (except alopecia)
  • Rate of all toxicities and serious unexpected side effects according to NCI CTCAE v2.0
  • Duration of disease control
  • Duration of chemotherapy-free interval
  • Progression-free survival
  • Overall survival
  • Time-to-treatment failure
  • Quality of life as assessed by EORTC QLQ-C30
  • Geriatric evaluation
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy and Bevacizumab With or Without Bevacizumab Maintenance Therapy in Treating Patients With Metastatic Colorectal Cancer
Official Title  ICMJE Multicenter Phase III Randomized Study of FOLFIRI Plus Bevacizumab Following or Not by a Maintenance Therapy With Bevacizumab in Patients With Non-Pretreated Metastatic Colorectal Cancer
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet known whether giving more than one drug (combination chemotherapy) is more effective when given with or without bevacizumab in treating patients with metastatic colorectal cancer.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy with or without bevacizumab to see how well it works in treating patients with metastatic colorectal cancer.

Detailed Description

OBJECTIVES:

Primary

  • Compare disease-control duration in patients with metastatic colorectal cancer receiving FOLFIRI chemotherapy in combination with bevacizumab with or without bevacizumab maintenance therapy.

Secondary

  • Determine objective response rate.
  • Determine non-hematologic grade 3-4 (except alopecia) toxicity rate.
  • Determine overall toxicity rate.
  • Determine duration of chemotherapy-free interval.
  • Determine progression-free survival.
  • Determine overall survival.
  • Determine time-to-treatment failure.
  • Determine quality of life (EORTC QLQ-C30).
  • Complete geriatric evaluation.

OUTLINE: This is a multicenter study. Patients are stratified according to cancer center, primary tumor (resected vs unresected), and Köhne criteria (low vs intermediate vs high). Patients are randomized to 1 of 2 treatment arms.

  • Arm A: Patients receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2. Chemotherapy treatment repeats every 2 weeks for 12 courses. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks during chemotherapy. Patients then receive bevacizumab maintenance therapy once every 2 weeks during the chemotherapy-free interval.
  • Arm B: Patients receive FOLFIRI chemotherapy and bevacizumab as in arm A. Patients receive no treatment during the chemotherapy-free interval.

In all arms, the chemotherapy treatment and the chemotherapy-free interval treatment repeats in the absence of disease progression during the chemotherapy portion or unacceptable toxicity. Patients who progress during the chemotherapy-free interval will receive 12 more courses of chemotherapy.

All patients complete quality of life questionnaires (QLQ-30) and patients ≥ 75 also complete the geriatric questionnaire at baseline and every 8 weeks during study treatment.

After completion of study treatment, patients are followed up every 8 weeks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Biological: bevacizumab
  • Drug: FOLFIRI regimen
  • Drug: fluorouracil
  • Drug: irinotecan hydrochloride
  • Drug: leucovorin calcium
Study Arms  ICMJE
  • Experimental: Maintenance with bevacizumab
    FOLFIRI + Avastin and during the chemotherapy-free interval maintenance with bevacizumab
    Interventions:
    • Biological: bevacizumab
    • Drug: FOLFIRI regimen
    • Drug: fluorouracil
    • Drug: irinotecan hydrochloride
    • Drug: leucovorin calcium
  • Active Comparator: No maintenance with bevacizumab
    FOLFIRI + Avastin and during the chemotherapy-free interval NO maintenance
    Interventions:
    • Biological: bevacizumab
    • Drug: FOLFIRI regimen
    • Drug: fluorouracil
    • Drug: irinotecan hydrochloride
    • Drug: leucovorin calcium
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 13, 2013)
492
Original Estimated Enrollment  ICMJE
 (submitted: August 1, 2009)
190
Actual Study Completion Date  ICMJE January 2018
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal cancer

    • Metastatic disease
  • Not a candidate for curative surgery
  • At least 1 tumor target measurable by RECIST criteria
  • No metastasis potentially resectable after receiving chemotherapy
  • No occlusive tumors
  • No macronodular peritoneal carcinomatosis
  • No known or suspected CNS metastases

PATIENT CHARACTERISTICS:

  • OMS status 0-2
  • Life expectancy ≥ 3 months
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN in the presence of hepatic metastases)
  • Creatinine ≤ 1.5 times ULN
  • Proteinuria ≤1 g
  • Not pregnant or nursing
  • No gastroduodenal ulcer, wound, or fractured bone
  • No acute or subacute intestinal occlusion or history of inflammatory bowel disease or large resection of small bowel
  • No clinically relevant coronary artery disease or a history of a myocardial infarction within the last 6 months
  • No uncontrolled hypertension while receiving chronic medication
  • No other malignancy within the past 5 years except for basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
  • No medical or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study

PRIOR CONCURRENT THERAPY:

  • See Patient Characteristics
  • No prior chemotherapy for metastatic disease

    • Adjuvant chemotherapy allowed provided it was completed > 6 months ago
  • No prior irinotecan or other antiangiogenic therapy
  • At least 4 weeks since surgery (except for diagnostic biopsy) or irradiation
  • No other drugs not allowed for medical reasons
  • Concurrent oral anticoagulants (e.g., coumadin, warfarin) allowed provided the INR is closely monitored

    • A change of anticoagulants to low-molecular weight heparin is preferred
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00952029
Other Study ID Numbers  ICMJE PRODIGE 9
FFCD-PRODIGE-9
FFCD-0802
EU-20912
EU-21030
EUDRACT-2008-007928-25
EUDRACT-2009-017996-11
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Federation Francophone de Cancerologie Digestive
Study Sponsor  ICMJE Federation Francophone de Cancerologie Digestive
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thomas Aparicio, Pr Hopital Avicenne BOBIGNY
PRS Account Federation Francophone de Cancerologie Digestive
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP