Overview

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