Efficacy and Safety of Aflibercept in Combination With FOLFIRI Chemotherapy as 1st Line Treatment for Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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One of the treatments generally used to treat this disease is a chemotherapy called FOLFIRI. The purpose of this study is to improve the efficacy of the chemotherapy by adding a protein, similar to immunoglobulins, aflibercept, and to assess their tolerance. Aflibercept is a protein that has already been studied in the treatment of metastatic colorectal cancers, in combination with a chemotherapy involving irinotecan in addition to 5FU (fluoropyrimidine) ( (FOLFIRI) as 2nd line treatment. It is marketed in Europe and it is authorized in the United States. Its addition to this chemotherapy combination has in fact brought about a benefit in terms of progression-free survival and overall survival. The purpose of the study is to evaluate the efficacy and tolerance of this combination rather in the initial approach to the treatment of metastatic colorectal cancers and hence to evaluate it as 1st line treatment

Official Title
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Efficacy and Safety of Aflibercept in Combination With FOLFIRI Chemotherapy as 1st Line Treatment for Patients With Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: FOLFIRI Protocol
* Drug: Aflibercept Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Overall state as per WHO (World Health Organization) ≤ 2 Life expectancy > 3 months Metastatic adenocarcinoma of the rectum or of the colon histologically proven on the primary tumor or a metastasis Unresectable metastasis (metastases) and/or inoperable patient Patient eligible for a 1st line treatment associating 5 FU-Irinotecan (FOLFIRI) and aflibercept At least one measurable target lesion according to RECIST criteria v1.1 not previously irradiated Absence of prior treatment of the metastatic disease. Prior adjuvant chemotherapy completed at least 12 months before the metastatic cancer diagnosis is authorized Satisfactory laboratory panel: Hb> 9 g/dl, polynuclear neutrophils > 1500 /mm3, platelets > 100,000/mm3, total bilirubin < 1.5 x UNL(upper normal limit), creatinine clearance > 50 mL/min (cockcroft-Gault formula - appendix 4), PAL (alkaline phosphatase) < 5 x UNL, AST (aspartate aminotransferase) and ALT (alanine aminotransferases) < 5 x UNL, GGT (gamma-glutamyltransferase) < 5 x UNL, Proteinuria on urine dipstick < 2+. If > 2+ test 24-hour proteinuria, which should be < 1 g Exclusion Criteria: Patients whose primary tumor is in place and presenting clinical symptoms (occlusion; hemorrhage) Brain metastases Gilbert's syndrome Uncontrolled hypercalcemia Hypertension not kept under control (SBP (Systolic Blood Pressure) >150 mmHg and DBP (Diastolic Blood Pressure) >100 mmHg) or history of hypertensive crisis or hypertensive encephalopathy Any unbalanced active disease over the last 6 months: liver failure, kidney failure, respiratory failure, congestive heart failure, unstable angina, myocardial infarction, significant arrhythmia (Patients treated by anticoagulants (coumadin, warfarin) are eligible if strict monitoring of the INR( international normalized ratio) is possible) Significant surgical intervention within the 28 days before the start of treatment Presence of active gastroduodenal ulcer, non-healed wound or bone fracture Antitumor treatments other than those included in the study (chemotherapy, targeted therapy, immunotherapy) History of malignant hemopathy or cancer except for those treated more than 5 years ago and considered healed, in situ carcinomas of the uterine cervix and treated skin cancers (except for melanoma) Pregnant or breast-feeding women, women of childbearing age not having taken a pregnancy test, absence of effective contraception in patients (men and/or women) of childbearing age Any contraindication of the drugs used in the study Impossible to meet the medical follow-up requirements of the study for geographic, social or psychological reasons

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FOLFIRI + Aflibercept<br>FOLFIRI and aflibercept (4 mg/m²) each 14 days until progression of disease | Drug: FOLFIRI Protocol<br>* injection of FOLFIRI and Aflibercept every 14 days until progression of disease<br>Drug: Aflibercept Injection<br>* injection of FOLFIRI and Aflibercept every 14 days until progression of disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Patients Alive and Progression-free 6 Months After Inclusion. | Progression was evaluated by CT scan, according to RECIST criteria (version 1.1) definition by the investigator. Death was also considered as an event (all causes). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions compared the little sum of diameters observed during the study (NADIR), or a measurable increase in a non-target lesion, or the appearance of new lesions | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival is defined as the time from the date of the patient's inclusion to the patient's death (all causes). For alive patients the date of the latest news is taken into account | Up to 2 years after the end of the treatment | 
| Progression-free Survival | The progression-free survival is the time from inclusion to the first radiological progression or death (all causes). For patients alive without progression date of last news will be considered. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions compared the little sum of diameters observed durin the study (NADIR), or a measurable increase in a non-target lesion, or the appearance of new lesions | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal cancer, Metastatic