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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

Phase 2/Phase 3
18 Years
Open (Enrolling)
Colorectal Cancer

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Trial Information

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



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


- 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.

Inclusion Criteria


- 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


- 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

- 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


- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-control duration

Outcome Time Frame:

one year after last patient included

Safety Issue:


Principal Investigator

Thomas Aparicio

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hopital Avicenne BOBIGNY


France: Agence Nationale de Sécurité du Médicament et des produits de santé

Study ID:




Start Date:

March 2010

Completion Date:

July 2015

Related Keywords:

  • Colorectal Cancer
  • stage IV colon cancer
  • stage IV rectal cancer
  • Colorectal Neoplasms