first line of treatment for metastatic colorectal cancer MedDRA version: 17.1 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Zaltrap
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Aflibercept
Other descriptive name: AFLIBERCEPT
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type:
Sponsors
Fédération Francophone de Cancérologie Digestive
Eligibility
Sex/Gender
All
Inclusion criteria
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 50 ml/min creatininemia 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Proportion of patients alive and without progression (radiological only) within 6 months (RECIST 1.1) according to the investigator;Secondary Objective: Tolerance of the LV5FU2-aflibercept combination (toxicities graded according to NCI-CTC V4.0) Quality of life: EORTC QLQ-C30 and time to final deterioration in quality of life Overall survival at 1 year and 3 years Best response (RECIST V1.1) to treatment according to the investigator at 1 year Proportion of patients alive and without progression (radiological only)within 6 months (RECIST 1.1) according to central reading Proportion of patients alive and without progression at 1 year (radiological only)within 6 months (RECIST 1.1) according to investigator Proportion of patients alive and without progression (RECIST 1.1) at 6 month ant at 1 year according to the investigator (Progression defined as clinical and/or radiological progression). Curative resectability at 1 year Prognostic nature of thymidylate synthase (TS) polymorphisms within at 6 months ;Primary end point(s): The main criterion for this study is the proportion of patients alive and not in progression within 6 months (+/- 15 days) after randomization. Progression will be evaluated by the investigator according to RECIST 1.1 criteria, based on imaging examinations carried out every 8 weeks, even if treatment courses are postponed. Clinical progressions not confirmed by imaging will not be included in the main judgement criterion. Patients with progression in imaging examinations before 6 months will be considered to be in progression at 6 months. Patients with surgery on their primary tumour before 6 months will be considered not to be in progression at 6 months. ;Timepoint(s) of evaluation of this end point: 6 month after randomiszation of each patient | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of patients alive and without progression within 6 months (RECIST 1.1) and 1 year according to the investigator reading. There are 2 progression définitions for investigator: either radiological progression alone (at 1 year), or clinical and/or radiological progression (at 6 month and 1 year) - Progression-free survival: defined as the delay between the date of randomization and the date of progression (RECIST 1.1 criteria, or death; Patients alive and without porgression will be censored at the date of point or date of the latest informative examination if it predates this. - Radiological progression-free survival at 6 months according to central reading (RECIST 1.1 criteria). Central reading of imaging evaluation examinations (TDM TAP or MRI with injection + thoracic TDM) during the first 6 months will be done. If central reading is impossible for some TDMs, the response according to RECIST v1.1 criteria will be the one given by the investigator. - Best response at 1 year: evaluated on the basis of all patient radiological examinations according to RECIST 1.1 criteria according to the investigator; it will be described according to the different categories (complete, partial response, stability or progression). - Overall survival at 1 year and 3 years : defined by the time between the date of randomization and the date of death; Alive patients will be censored at the date of point or the date of latest news if it precedes this. - Tolerance: evaluated by toxicities observed and graded according to NCI-CTC V4.0 ; the following toxicities will particularly be examined: grade 2 or higher for cutaneous toxicities; weight evolution and WHO performance index will be described as well as SAEs. - Quality of life: measured via the EORTC QLQ-C30 questionnaire, completed at baseline and at each evaluation visit during treatment, then during follow-up visits after the treatment stop (every 3 months for 2 years, then every 6 months for 1 ye | — |
Countries
France
Contacts
Public ContactChef de Projet
Fédération Francophone de Cancérologie Digestive
Outcome results
None listed