Aflibercept +/- LV5FU2 in First Line of Non-resectalbe Metastatic Colorectal Cancers

• Status: Recruiting
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This is what the FFCD 11-01 - PRODIGE 25 trial proposes to study, as a preliminary for strategic studies evaluating the usefulness of including targeted therapeutics from the first line with aflibercept +/- LV5FU2.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Federation Francophone de Cancerologie Digestive
• Treatments: Aflibercept

Criteria

Inclusion Criteria:

• Age ≥ 65 years

• General condition WHO ≤ 2

• Metastatic rectal or colonic adenocarcinoma, histologically proved on the primary tumour or a metastasis

• Metastases non-resectable and/or patient inoperable

• patients where a single agent chemotherapy combined with an anti-angiogenic agent is an appropriate approach

• 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 > or = 9 g/dl, polynuclear neutrophils > or = 1,500/mm3, platelets > or =100,000/mm3, total bilirubin < or = 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

• Proteinuria (strip) < 2+; if > or = 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

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.

• 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)

• Macronodular peritoneal carcinosis (risk of perforation)

• 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