Clinical trial NCT02181556: Efficacy and Safety of Aflibercept in Combination With FOLFIRI Chemotherapy as 1st Line Treatment for Patients With Metastatic Colorectal Cancer
Official title: Efficacy and Safety of Aflibercept in Combination With FOLFIRI Chemotherapy as 1st Line Treatment for Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: colorectal cancer
Metastatic
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
First posted: 2014-07-04
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Rate of Patients Alive and Progression-free 6 Months After Inclusion.
timeFrame: 6 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 2 years after the end of the treatment
measure: Progression-free Survival
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU - Hôtel Dieu
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Dijon
country: France
facility: CHU - Hôpital François Mitterand
city: Lyon
country: France
facility: Clinique Jean Mermoz
city: Marseille
country: France
facility: La Timone
city: Paris
country: France
facility: Hôpital Européen Geaorge Pompidou (HEGP)
city: Paris
country: France
facility: Hôpital La Pitié Salpetière
city: Tours
country: France
facility: Hôpital Trousseau
Study officials:
affiliation: Fédération Francophone de Cancérologie Digestive
name: Julien TAIEB, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lapeyre-Prost A, Pernot S, Sigrand J, Le Malicot K, Mary F, Aparicio T, Dahan L, Caroli-Bosc FX, Lecomte T, Doat S, Marthey L, Desrame J, Lepage C, Taieb J. Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302). Clin Colorectal Cancer. 2020 Dec;19(4):285-290. doi: 10.1016/j.clcc.2020.06.003. Epub 2020 Jun 12.