Efficacy and Safety of Aflibercept in Combination With FOLFIRI Chemotherapy as 1st Line Treatment for Patients With Metastatic Colorectal Cancer
Condition: Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: FOLFIRI Protocol; Aflibercept Injection
Intervention description: injection of FOLFIRI and Aflibercept every 14 days until progression of disease; injection of FOLFIRI and Aflibercept every 14 days until progression of disease
Intervention MeSH terms: Aflibercept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: colorectal cancer; Metastatic

Summary:

      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
    

Eligibility criteria:

        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