Evaluation of Bevacizumab in Combination With First-Line Chemotherapy in Patients Aged 75 Years of Older With Metastatic Colorectal Adenocarcinoma (Prodige20)

Study Overview
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Brief Summary
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To evaluate tolerance to and efficacy of bevacizumab in the treatment of MCRC in elderly patients, we propose a phase II randomised study comparing a chemotherapy + bevacizumab arm with a chemotherapy alone arm in the first-line treatment of MCRC in patients aged 75 years and older. This study is destined to continue as a phase III trial if both arms meet the selection criteria to show or not the benefits of treatment with bevacizumab combined with chemotherapy.

Official Title
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Evaluation of Bevacizumab in Combination With First-Line Chemotherapy in Patients Aged 75 Years of Older With Metastatic Colorectal Adenocarcinoma

Conditions
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Metastatic Colorectal Adenocarcinoma

Intervention / Treatment
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* Drug: LV5FU2 simplified, FOLFOX 4 simplified, FOLFIRI modified
* Drug: LV5FU2 simplified,FOLFOX 4 simplified, FOLFIRI modified, Bevacizumab 5 mg/kg/ 2 weeks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 75 years or older ECOG ≤2 histologically proven unresectable metastatic colorectal adenocarcinoma Measurable lesion according to RECIST criteria Absence of prior chemotherapy for metastatic disease. Adjuvant chemotherapy following resection of the primary tumor is authorized if completed more than 6 months previously Patients treated with anticoagulants (coumadin, warfarin) can be included if close surveillance of the INR can be ensured. A change to low-molecular-weight heparin is preferable as long as the indications are respected Completed geriatric self-questionnaire Completed Team geriatric questionnaire (including Spitzer QoL Index) Written informed consent Exclusion Criteria: Estimated life expectancy < 3 months Non-resolved intestinal occlusion or sub-occlusion Cerebral metastasis Other evolutive malignant tumor (non-stabilized cancer for less than 2 years) Evolutive gastroduodenal ulcer, wound or bone fracture Active heart disease: uncontrolled hypertension, myocardial infarction In the previous 6 months, angina, non-compensated congestive heart failure Major surgery, except for biopsy, or irradiation in the 4 weeks preceding the start of treatment Polynuclear neutrophils <1500/mm3, platelets <100 000/mm3 or 24-h proteinuria > 1g History of arterial thromboembolic event (cerebrovascular accident, transient ischemic attack, subarachnoid hemorrhage) in the 12 months preceding the first dose of bevacizumab History of distal or visceral ischemia ≥ grade 2 in the 12 months preceding the first dose of bevacizumab History of life-threatening pulmonary embolism in the 6 months preceding the first dose of bevacizumab Impossibility to ensure regular follow-up

Ages Eligible for Study
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Minimum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: chimiotherapy alone<br>LV5FU2 simplified, 5-fluorouracil/leucovorin with oxaliplatin 4 (FOLFOX) simplified, fluorouracil, leucovorin, and irinotecan(FOLFIRI) modified. | Drug: LV5FU2 simplified, FOLFOX 4 simplified, FOLFIRI modified<br> <br> |
| Experimental: chemiotherapy + bevacizumab 5 mg/kg/ 2 weeks<br>LV5FU2 simplified, FOLFOX 4 simplified, FOLFIRI modified. Bevacizumab 5 mg/kg/ 2 weeks | Drug: LV5FU2 simplified,FOLFOX 4 simplified, FOLFIRI modified, Bevacizumab 5 mg/kg/ 2 weeks<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial examination | thoraco-abdomino-pelvic tomodensitometry or thoracic tomodensitometry and abdomino-pelvic MRI with identification and measurement of the target tumors according to RECIST (Response Evaluation Criteria in Solid Tumors )criteria. | 21 days before the first course of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial examination | Medical history, clinical examination (HR, arterial blood pressure , temperature, weight, height, Eastern Cooperative Oncology Group performance status), measurement of body surface area, ECG completion of questionnaire by the patient (annexe 1), completion of geriatric questionnaire team (annexe 2) biological examination including: full blood count-platelets blood electrolyte panel, creatinemia Albumin ASAT, ALAT, PAL, GGT, total and conjugated bilirubin CEA, CA 19.9, LDH markers balanced INR for patients on AVK Urinary dip with 24-hour proteinuria if > 1+ Measurement of creatinine clearance using the Cockcroft formula (in men: (140-age) x weight (kg)/0.814 x creatinemia (μmol), in women: (140-age) x weight (kg)/0.85 x creatinemia (μmol)), In the absence of a cardiological examination in the year before or in the case of a history of severe cardiovascular disease: consultation in cardiology. | 14 days before inclusion |