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

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
FOLFIRI Protocol
Aflibercept Injection
Sponsored by
Federation Francophone de Cancerologie Digestive
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring colorectal cancer, Metastatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU - Hôtel Dieu
  • Hôpital Avicenne
  • CHU - Hôpital François Mitterand
  • Clinique Jean Mermoz
  • La Timone
  • Hôpital Européen Geaorge Pompidou (HEGP)
  • Hôpital La Pitié Salpetière
  • Hôpital Trousseau

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FOLFIRI + Aflibercept

Arm Description

FOLFIRI and aflibercept (4 mg/m²) each 14 days until progression of disease

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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

Full Information

First Posted
July 2, 2014
Last Updated
May 12, 2021
Sponsor
Federation Francophone de Cancerologie Digestive
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1. Study Identification

Unique Protocol Identification Number
NCT02181556
Brief Title
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

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
October 2014 (Actual)
Primary Completion Date
February 2017 (Actual)
Study Completion Date
July 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Federation Francophone de Cancerologie Digestive

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
colorectal cancer, Metastatic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FOLFIRI + Aflibercept
Arm Type
Experimental
Arm Description
FOLFIRI and aflibercept (4 mg/m²) each 14 days until progression of disease
Intervention Type
Drug
Intervention Name(s)
FOLFIRI Protocol
Intervention Description
injection of FOLFIRI and Aflibercept every 14 days until progression of disease
Intervention Type
Drug
Intervention Name(s)
Aflibercept Injection
Intervention Description
injection of FOLFIRI and Aflibercept every 14 days until progression of disease
Primary Outcome Measure Information:
Title
Rate of Patients Alive and Progression-free 6 Months After Inclusion.
Description
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
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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
Time Frame
Up to 2 years after the end of the treatment
Title
Progression-free Survival
Description
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
Time Frame
up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julien TAIEB, PhD
Organizational Affiliation
Fédération Francophone de Cancérologie Digestive
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU - Hôtel Dieu
City
Angers
Country
France
Facility Name
Hôpital Avicenne
City
Bobigny
ZIP/Postal Code
93000
Country
France
Facility Name
CHU - Hôpital François Mitterand
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Clinique Jean Mermoz
City
Lyon
Country
France
Facility Name
La Timone
City
Marseille
ZIP/Postal Code
13000
Country
France
Facility Name
Hôpital Européen Geaorge Pompidou (HEGP)
City
Paris
ZIP/Postal Code
75020
Country
France
Facility Name
Hôpital La Pitié Salpetière
City
Paris
Country
France
Facility Name
Hôpital Trousseau
City
Tours
ZIP/Postal Code
37044
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
32921581
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.
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Efficacy and Safety of Aflibercept in Combination With FOLFIRI Chemotherapy as 1st Line Treatment for Patients With Metastatic Colorectal Cancer

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