1st Line Chemotherapy Alone or With Bevacizumab in Treating Older Patients With Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed 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.
    

Intervention name(s): Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen); Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen) + bevacizumab
Intervention type(s): Drug; Drug
Intervention MeSH terms: Leucovorin; Bevacizumab; Fluorouracil; Oxaliplatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the colon; stage IVA colon cancer; stage IVB colon cancer; adenocarcinoma of the rectum; stage IVA rectal cancer; stage IVB rectal cancer