Study to evaluate aflibercept (efficacity and toxicity) with a chemotherapy by 5 FU in first line of treatment for patients with a metastatic colorectal cancer

Phase 1

• Conditions: first line of treatment for metastatic colorectal cancer; MedDRA version: 17.1Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-001837-10-FR
• Lead Sponsor: Fédération Francophone de Cancérologie Digestive

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-07
• Last Update Posted: 13 March 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Age = 65 years
General condition WHO = 2
Metastatic rectal or colonic adenocarcinoma, histologically proved on the primary tumour or a metastasis, non-resectable and/or patient inoperable
patients where a single agent chemotherapy combined with an anti-angiogenic agent is an appropriate approach
None or por symptomatic metastasis
At least one measurable target according to RECIST v1.1 criteria, no previously irradiated
No previous treatment of the metastatic disease. Previous chemotherapy in an adjuvant situation completed 6 months or more before diagnosis of the metastasis is authorized.
Adequate biological examination: Hb > 9 g/dl, polynuclear neutrophils > 1,500/mm3, platelets > 100,000/mm3, total bilirubin < 1.5 x UNL, creatinine clearance, calculated according to Cockroft-Gault formula, > 50 ml/min creatininemia < 1.5 x UNL, ALP < 5 x UNL, transaminases < 5 x ULN, GGT< 5 x UNL , GGT < 5 x LSN
Proteinuria (strip) < 2+; if > 2+, test proteinuria over 24 hours which must be = 1 g.
Central genotyping of thymidylate synthase (TS) in blood DNA
Patients treated with anticoagulants (coumadin, warfarin) can be included if the INR can be closely monitored. A change in anticoagulant treatment for low molecular weight heparin is preferable in order to respect indications
Signed written informed consent obtained prior to inclusion

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 118

Exclusion Criteria

Patients with a primary tumour in place and presenting clinical symptoms (occlusion, haemorrhage)
History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
Macronodular peritoneal carcinosis (risk of perforation)
Uncontrolled hypercalcemia
Uncontrolled hypertension (SBP > 150 mmHg and DBP > 100 mmHg) or history of hypertensive attacks or hypertensive encephalopathy
Any progressive pathology not balanced over the past 6 months: hepatic insufficiency, renal insufficiency, respiratory insufficiency,
Any of the following within 6 months prior to inclusion: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack.
Any of the following within 3 months prior to inclusion: Grade 3-4 gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event, wound or fractured bone
Major surgery during the 28 days preceding the start of treatment
Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.
Treatment with concomitant anticonvulsivant agents that are CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.
Anti-tumoral treatments other than the trial treatments (chemotherapy, targeted therapy, immunotherapy)
Known DPD deficit
Prior history of malignant haemopathy or cancer except those treated more than 5 years ago and considered to be cured, in situ cervical carcinomas and treated skin cancers (excluding melanoma)
Patients on new oral anticoagulant therapy (rivaroxaban XARELTOR, apixaban ELIQUIS, dagigatran PRADAXA except if relay by vitamine K antagonist therapy)
Any contraindication to the treatments used in the trial
Impossibility of undergoing medical monitoring during the trial for geographic, social or psychological reasons

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified