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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier:
NCT01417494
First received: August 13, 2011
Last updated: March 3, 2014
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen)
Drug: Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen) + bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Federation Francophone de Cancerologie Digestive:

Primary Outcome Measures:
  • Efficacy, in terms of objective response or tumoral stability by RECIST criteria [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Deterioration in the Spitzer QoL Index score of ≥ 2 points at baseline and at 4 months [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Tolerance, in terms of no grade 4 arterial hypertension, grade 3-4 thromboembolic event, grade 3-4 cardiac insufficiency, and hospitalization not related to chemotherapy [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
  • Time to deterioration of autonomy [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Survival with no deterioration of autonomy [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 102
Study Start Date: July 2011
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy associated with bevacizumab
Chemotherapy (FOLFIRI, FOLFOX, LV5FU2) associated with bevacizumab
Drug: Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen) + bevacizumab
Active Comparator: Chemotherapy
Chemotherapy (FOLFIRI, FOLFOX, LV5FU2)
Drug: Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen)

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.

  Eligibility

Ages Eligible for Study:   75 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01417494

Locations
France
Hôpital Avicenne
Bobigny, France, 93000
Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Roche Pharma AG
Investigators
Principal Investigator: Thomas Aparicio Hopital Avicenne
  More Information

Additional Information:
No publications provided

Responsible Party: Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier: NCT01417494     History of Changes
Other Study ID Numbers: CDR0000706869, FFCD-PRODIGE-20, EU-21120, 2010-022080-34
Study First Received: August 13, 2011
Last Updated: March 3, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Federation Francophone de Cancerologie Digestive:
adenocarcinoma of the colon
stage IVA colon cancer
stage IVB colon cancer
adenocarcinoma of the rectum
stage IVA rectal cancer
stage IVB rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Adenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Bevacizumab
Oxaliplatin
Fluorouracil
Leucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on September 18, 2014