Evaluation of the Efficacy and the Safety of FOLFIRINOX3 Bevacizumab Treatment in Patients With Colorectal Cancer (FOLFIRINOX 3) (FOLFIRINOX3)

Phase I / II Study Evaluating the Efficacy and Safety of FOLFIRINOX3 Bevacizumab Treatment in Patients With Colorectal Cancer Who Have Failed With Standard Chemotherapy Protocols (FOLFIRINOX 3)

In patients in progression after oxaliplatin and irinotecan, the study FOLFIRINOX 3 proposes to evaluate the interest of modifying the standard pattern of administration of the molecule of irinotecan in order to make it more efficient. In combination with other chemotherapy drugs (5-fluorouracil, oxaliplatin, folinic acid and bevacizumab), irinotecan will be administered at the beginning and end of each cycle of chemotherapy, whereas it is normally administered at one time in the regimen. standard of treatment.

The hypothesis of this study is an increase in the objective response rate at 2 months of 10 to 30% with a scheme by FOLFIRINOX3 - bevacizumab compared to an optimal treatment to date by FOLFIRINOX-bevacizumab.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: FOLFIRINOX Bevacizumab

Detailed Description

Primary objective

• Main objective of phase I: To evaluate the acute toxicity of treatment with FOLFIRINOX 3 - bevacizumab
• Main objective of phase II: To evaluate the efficacy of treatment with FOLFIRINOX 3 - bevacizumab in terms of objective response according to the RECIST criteria.

Secondary objectives

• To evaluate the efficacy of treatment with FOLFIRINOX 3 - bevacizumab in terms of objective response according to the criteria of CHOI, progression-free survival (PFS) and overall survival (OS)
• To evaluate the late toxicity of treatment with FOLFIRINOX 3 - bevacizumab
• Evaluate the quality of life

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: François Ghiringhelli, PU PH; Phone Number: 03 80 73 77 53; Email: FGhiringhelli@cgfl.fr

Study Locations

• France
  • Dijon, France, 21000
    • Centre Georges Francois Leclerc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men or women
2. Age ≥ 18 years
3. Performance status of 0 or 1 (WHO ECOG Index)
4. Patient with metastatic colon cancer
5. History of chemotherapy treatment including oxaliplatin, irinotecan, antiangiogenic (bevacizumab or aflibercept) and anti-EGFR if indicated
6. Patient eligible for treatment with FOLFIRINOX bevacizumab
7. Tumor evaluation (thoraco-abdominopelvic CT scan) performed within 4 weeks before inclusion with at least one measurable lesion according to RECIST criteria 1.1
8. Patient able and able to abide by the protocol throughout the study, including treatment, visits, scheduled examinations and follow-up.

9. Biological values within the following limits:

   • Bilirubinemia ≤ 1.5 times the upper limit of normal (N)
   • ASAT and ALAT ≤ 5 N
   • Creatinine ≤ 1.5 N and creatinine clearance> 60 mlmin
   • Neutrophils ≥ 1.5. 109 / L
   • Platelets ≥ 150. 109 / L
   • Hemoglobin ≥ 9 g / dL (patients can be included even if they have been transfused).
   • Albuminémie≥30g / L
   • Hepatitis B, C and HIV negative serologies
10. Information note given and signed informed consent
11. Patient affiliated to a social security scheme
12. Women must have effective contraception and must have a negative pregnancy test at the time of entry into the study or must no longer be of childbearing age (ie, postmenopausal, after 60 years and no menstruation for ≥1 year without any other medical cause, OR history of hysterectomy, OR history of bilateral oophorectomy),

Exclusion Criteria:

1. Other cancer in the 5 years prior to entry into the trial or concomitant (except in situ cancer of the cervix or basal cell carcinoma of the skin).
2. Presence of cerebral metastasis (s)
3. Prognosis estimated <3 months
4. Presence of a contraindication to bevacizumab (major surgery in the previous 28 days, risk of arterial thrombosis, risk of haemorrhage, deep vein thrombosis without effective anticoagulant therapy or unbalanced anticoagulant therapy)
5. History of grade 4 toxicity to oxaliplatin, irinotecan, 5FU or bevacizumab
6. Persistence of neuropathy greater than a grade 1
7. Hypersensitivity to one of the compounds of the treatments
8. Participation in course or within 30 days prior to entry into the study to another therapeutic trial with an experimental molecule.
9. Demonstration of a DPYD and / or UGT1A1 mutation
10. Unbalanced serious illness, underlying infection that may prevent the patient from receiving treatment
11. Pregnancy (compulsory pregnancy test at baseline), breastfeeding or lack of effective contraception for men and women of childbearing age
12. Psychiatric illness compromising understanding of information or completion of study
13. Patient under tutorship, curatorship or court of justice
14. Inability to sign informed consent or to undergo medical follow-up of the trial for geographical, social or psychological reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Administration of chemotherapy molecules; The treatment period is divided into 15-day periods. Schema of the administration to the treatments which will proceed in the same way with each cycle: Bevacizumab (5 mg/kg; during 30 min) + Oxaliplatine (85 mg/m2, during 2 hours) + Acide folinique (400 mg/m2) or Levofolinate de calcium (200 mg/m2) AND Irinotecan (during 2 hours) + 5-fluorouracile (2400 mg/m2 ; 46 hours) + Irinotecan (1 hour)

Drug: FOLFIRINOX Bevacizumab; In phase 1, the goal is to define the DLT (maximum tolerated dose). 3 levels of doses will be evaluated with a different dose of irinotecan in each level.; Level -1: Bevacizumab + Oxaliplatine + Acide folinique + Irinotecan: 60mg / m2; Level 0: Bevacizumab + Oxaliplatine + Acide folinique +Irinotecan: 70mg / m2; Level 1: Bevacizumab + Oxaliplatine + Acide folinique +Irinotecan: 90mg / m2 The inclusion of patients will start at level 0. Dose-limiting toxicities will be identified during the first 2 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Acute toxicities as a Measure of treatment specific Safety and Tolerability	Acute toxicities will be assessed according to the NCI CTCAE v4.03	each chemotherapy cycle (15 days) up to progression (6 months on average)

Collaborators and Investigators

• Sponsor: Centre Georges Francois Leclerc

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2018
• Primary Completion (Estimated): November 21, 2024
• Study Completion (Estimated): November 21, 2024

Study Registration Dates

• First Submitted: January 2, 2019
• First Submitted That Met QC Criteria: January 3, 2019
• First Posted (Actual): January 7, 2019

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: FOLFIRINOX3 Bevacizumab
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Folfirinox
• Other Study ID Numbers: FOLFIRINOX3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No