Combination Chemotherapy and Bevacizumab With or Without Bevacizumab Maintenance Therapy in Treating Patients With Metastatic Colorectal Cancer
This study is currently recruiting participants.
Verified June 2013 by Federation Francophone de Cancerologie Digestive
Sponsor:
Federation Francophone de Cancerologie Digestive
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier:
NCT00952029
First received: August 1, 2009
Last updated: June 13, 2013
Last verified: June 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Colorectal Cancer |
Biological: bevacizumab Drug: FOLFIRI regimen Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
Resource links provided by NLM:
Drug Information available for:
Fluorouracil
Leucovorin calcium
Levoleucovorin
Irinotecan
Irinotecan hydrochloride
Bevacizumab
U.S. FDA Resources
Further study details as provided by Federation Francophone de Cancerologie Digestive:
Primary Outcome Measures:
- Disease-control duration [ Time Frame: one year after last patient included ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 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 ]
| Estimated Enrollment: | 492 |
| Study Start Date: | March 2010 |
| Estimated Study Completion Date: | July 2015 |
| Estimated Primary Completion Date: | July 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval maintenance with bevacizumab
|
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
|
Biological: bevacizumab Drug: FOLFIRI regimen Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00952029
Locations
| France | |
| Hopital Bichat - Claude Bernard | Recruiting |
| Paris, France, 75018 | |
| Contact: Contact Person 33-1-4895-5431 Thomas.aparicio@avc.aphp.fr | |
Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Investigators
| Principal Investigator: | Thomas Aparicio | Hopital Avicenne BOBIGNY |
More Information
Additional Information:
No publications provided
| Responsible Party: | Federation Francophone de Cancerologie Digestive |
| ClinicalTrials.gov Identifier: | NCT00952029 History of Changes |
| Other Study ID Numbers: | CDR0000636983, FFCD-PRODIGE-9, FFCD-0802, EU-20912, EU-21030, EUDRACT-2008-007928-25, EUDRACT-2009-017996-11 |
| Study First Received: | August 1, 2009 |
| Last Updated: | June 13, 2013 |
| Health Authority: | France: Agence Nationale de Sécurité du Médicament et des produits de santé |
Keywords provided by Federation Francophone de Cancerologie Digestive:
|
stage IV colon cancer stage IV 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 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 Growth Substances |
ClinicalTrials.gov processed this record on June 18, 2013