Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier:
NCT00952029
First received: August 1, 2009
Last updated: March 3, 2014
Last verified: March 2014

August 1, 2009
March 3, 2014
March 2010
July 2015   (final data collection date for primary outcome measure)
Disease-control duration [ Time Frame: one year after last patient included ] [ Designated as safety issue: No ]
Objective response rate at 8 months according to RECIST criteria or MRI scan [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00952029 on ClinicalTrials.gov Archive Site
  • Objective response rate [ Time Frame: one year after last patient is included ] [ Designated as safety issue: No ]
  • Rate of non-hematologic grade 3-4 toxicities (except alopecia) [ Time Frame: one year after last patient is included ] [ Designated as safety issue: Yes ]
  • Overall toxicity rate [ Time Frame: one year after last patient is included ] [ Designated as safety issue: Yes ]
  • Duration of chemotherapy-free interval [ Time Frame: one year after last patient is included ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: one year after last patient is included ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: one and 2 year after last patient is included ] [ Designated as safety issue: No ]
  • Time-to-treatment failure [ Time Frame: one year after last patient is included ] [ Designated as safety issue: No ]
  • Quality of life as assessed by EORTC QLQ-C30 [ Time Frame: one year after last patient is included ] [ Designated as safety issue: No ]
  • Geriatric evaluation [ Time Frame: one year after last patient is included ] [ Designated as safety issue: No ]
  • Rate of non-hematologic grade 3-4 toxicities (except alopecia) [ Designated as safety issue: Yes ]
  • Rate of all toxicities and serious unexpected side effects according to NCI CTCAE v2.0 [ Designated as safety issue: Yes ]
  • Duration of disease control [ Designated as safety issue: No ]
  • Duration of chemotherapy-free interval [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Time-to-treatment failure [ Designated as safety issue: No ]
  • Quality of life as assessed by EORTC QLQ-C30 [ Designated as safety issue: No ]
  • Geriatric evaluation [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Combination Chemotherapy and Bevacizumab With or Without Bevacizumab Maintenance Therapy in Treating Patients With Metastatic Colorectal Cancer
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

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Colorectal Cancer
  • Biological: bevacizumab
  • Drug: FOLFIRI regimen
  • Drug: fluorouracil
  • Drug: irinotecan hydrochloride
  • Drug: leucovorin calcium
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
492
July 2016
July 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00952029
CDR0000636983, FFCD-PRODIGE-9, FFCD-0802, EU-20912, EU-21030, EUDRACT-2008-007928-25, EUDRACT-2009-017996-11
Yes
Federation Francophone de Cancerologie Digestive
Federation Francophone de Cancerologie Digestive
Not Provided
Principal Investigator: Thomas Aparicio Hopital Avicenne BOBIGNY
Federation Francophone de Cancerologie Digestive
March 2014

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