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

Phase 2

Completed

• Conditions: Metastatic Colorectal Adenocarcinoma
• Interventions: Drug: LV5FU2 simplified,FOLFOX 4 simplified, FOLFIRI modified, Bevacizumab 5 mg/kg/ 2 weeks; Drug: LV5FU2 simplified, FOLFOX 4 simplified, FOLFIRI modified

• Registration Number: NCT01900717
• Lead Sponsor: Centre Hospitalier Universitaire Dijon

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-07
• Study First Submitted: 2013-07-12
• Study First Submitted QC: 2013-07-12
• Study First Posted: 2013-07-16
• Primary Completion: 2015-05
• Study Completion: 2016-03
• Status Verified: 2018-12
• Last Update Submitted: 2018-12-26
• Last Update Posted: 2018-12-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 102

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
chemiotherapy + bevacizumab 5 mg/kg/ 2 weeks	LV5FU2 simplified,FOLFOX 4 simplified, FOLFIRI modified, Bevacizumab 5 mg/kg/ 2 weeks	* LV5FU2 simplified, * FOLFOX 4 simplified, * FOLFIRI modified. * Bevacizumab 5 mg/kg/ 2 weeks
chimiotherapy alone	LV5FU2 simplified, FOLFOX 4 simplified, FOLFIRI modified	* LV5FU2 simplified, * 5-fluorouracil/leucovorin with oxaliplatin 4 (FOLFOX) simplified, * fluorouracil, leucovorin, and irinotecan(FOLFIRI) modified.

Primary Outcome Measures

Name	Time	Method
Initial examination	21 days before the first course of treatment	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.

Secondary Outcome Measures

Name	Time	Method
Initial examination	14 days before inclusion	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.

Trial Locations

Locations (1)

CHU de Dijon; 🇫🇷 Dijon, France