Trial Information

Evaluation of Bevacizumab Combined With First Line Chemotherapy in Patients Aged 75 and Over Suffering From Metastatic Colorectal Adenocarcinoma. Phase II Randomized - Intergroup Trial: FFCD, FNCLCC, GERICO

OBJECTIVES:

Primary

- To evaluate composite efficacy and safety, in terms of objective response or tumoral
stability by RECIST criteria and no deterioration in the Spitzer QoL Index score of ≥ 2
points at 4 months, in older patients with unresectable metastatic colorectal
adenocarcinoma treated with bevacizumab and first-line chemotherapy.

- To evaluate tolerance, in terms of no grade 4 arterial hypertension, grade 3-4
thromboembolic event, grade 3-4 cardiac insufficiency, and hospitalization not linked
to chemotherapy, in these patients.

Secondary

- To evaluate toxicity in these patients.

- To assess time to deterioration of autonomy in these patients.

- To assess survival with no deterioration of autonomy of these patients.

- To evaluate time to deterioration of quality of life of these patients.

- To evaluate percentage of patients who received at least 2/3 of the protocol treatment
at month 4.

- To assess time to treatment failure in these patients.

- To assess progression-free survival and global survival of these patients.

Tertiary

- To test for predictive factors of treatment success identified during the geriatric
evaluation, according to the main judgment criterion, and analysis of the evolution of
geriatric parameters during follow-up int these patients. (Exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to chemotherapy
(monotherapy vs double chemotherapy), primary tumor (resected vs non-resected), and
quality-of-life score evaluated by the Spitzer QoL Index (0-3 vs 4-7 vs 8-10). Patients are
randomized to 1 of 2 treatment arms.

- Arm A: Patients receive 1 of the following regimens according to the discretion of the
investigator:

- Simplified LV5FU2 comprising leucovorin calcium IV over 2 hours on days 1 and 15
and fluorouracil IV over 46 hours beginning on days 1 and 15.

- FOLFIRI comprising leucovorin calcium IV over 2 hours on days 1 and 15; irinotecan
hydrochloride IV over 2 hours on days 1 and 15; and fluorouracil IV over 46 hours
beginning on days 1 and 15.

- FOLFOX4 comprising oxaliplatin IV over 2 hours on days 1 and 15; leucovorin
calcium IV over 2 hours on days 1 and 15; and fluorouracil IV over 46 hours
beginning on days 1 and 15.

All treatment regimens repeat every 4 weeks for at least 6 months in the absence of disease
progression or unacceptable toxicity.

- Arm B: Patients receive chemotherapy as in arm A. Patients also receive bevacizumab IV
over 90 minutes on days 1 and 15. Treatment repeats every 4 weeks for at least 6 months
in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed periodically. Blood specimens are collected for evaluation of
the quantification of circulating cells for early prediction of response to treatment.

After completion of study therapy, patients are followed up every 2-3 months.