1st Line Chemotherapy Alone or With Bevacizumab in Treating Older Patients With Metastatic Colorectal Cancer

Federation Francophone de Cancerologie Digestive

Status and phase

Completed

Phase 2

Conditions

Colorectal Cancer

Treatments

Drug: Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen)

Drug: Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen) + bevacizumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01417494

CDR0000706869

EU-21120 (Other Identifier)

FFCD-PRODIGE-20 (Other Identifier)

2010-022080-34 (EudraCT Number)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving bevacizumab together with combination chemotherapy may be a better way to block tumor growth. It is not yet known whether combination chemotherapy is more effective when given together with or without bevacizumab in treating patients with colorectal cancer.

PURPOSE: This randomized phase II trial is studying the side effects of giving bevacizumab together with first-line chemotherapy and to see how well it works in treating older patients with metastatic colorectal cancer.

Full description

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.

Enrollment

102 patients

Sex

All

Ages

75 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed metastatic colorectal adenocarcinoma
- Unresectable disease
Measurable disease by RECIST criteria
No cerebral metastasis

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 3 months
Polynuclear neutrophils > 1,500/mm^3
Platelet count > 100,000/mm^3
Proteinuria ≤ 1 g on 24-hour urine collection
No unresolved intestinal occlusion or subocclusion
No other progressive or unstabilized malignant tumor within the past 2 years
No progressive gastroduodenal ulcer, wound, or bone fracture
No active cardiac disease including any of the following:
- Hypertension not adequately controlled
- Myocardial infarction within the past 6 months
- Poorly controlled angina
- Decompensated congestive cardiac insufficiency
No history of arterial thromboembolism or any of the following within the past 12 months:
- Cerebrovascular accident
- Transient ischemic attack
- Subarachnoid hemorrhage
No history of distal or visceral ischemic arterial pathology ≥ grade 2 within the past 12 months
No history of life-threatening pulmonary embolism within the past 6 months
Must have completed the geriatric self-administered questionnaire and the geriatric "team" questionnaire (including the Spitzer QoL Index)

PRIOR CONCURRENT THERAPY:

No prior chemotherapy for metastatic disease
- More than 6 months since adjuvant chemotherapy after resection of the primary tumor
More than 4 weeks since major surgery, excluding biopsy
More than 4 weeks since radiotherapy