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

NCT03795311 | Active Not Recruiting Phase 1

• 1 other identifier: FOLFIRINOX3
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

FOLFIRINOX3 Bevacizumab

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (1)

Administration of chemotherapy molecules

EXPERIMENTAL

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

Interventions

FOLFIRINOX Bevacizumab DRUG

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.

Administration of chemotherapy molecules

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women
• Age ≥ 18 years
• Performance status of 0 or 1 (WHO ECOG Index)
• Patient with metastatic colon cancer
• History of chemotherapy treatment including oxaliplatin, irinotecan, antiangiogenic (bevacizumab or aflibercept) and anti-EGFR if indicated
• Patient eligible for treatment with FOLFIRINOX bevacizumab
• Patient able and able to abide by the protocol throughout the study, including treatment, visits, scheduled examinations and follow-up.
• 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

You may not qualify if:

• 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).
• Presence of cerebral metastasis (s)
• Prognosis estimated \<3 months
• 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)
• History of grade 4 toxicity to oxaliplatin, irinotecan, 5FU or bevacizumab
• Persistence of neuropathy greater than a grade 1
• Hypersensitivity to one of the compounds of the treatments
• Participation in course or within 30 days prior to entry into the study to another therapeutic trial with an experimental molecule.
• Demonstration of a DPYD and / or UGT1A1 mutation
• Unbalanced serious illness, underlying infection that may prevent the patient from receiving treatment
• Pregnancy (compulsory pregnancy test at baseline), breastfeeding or lack of effective contraception for men and women of childbearing age
• Psychiatric illness compromising understanding of information or completion of study
• Patient under tutorship, curatorship or court of justice
• Inability to sign informed consent or to undergo medical follow-up of the trial for geographical, social or psychological reasons.

Sponsors & Collaborators

• Centre Georges Francois Leclerc: lead

Study Sites (1)

Centre Georges François Leclerc

Dijon, 21000, France

Location

Related Publications (1)

• Bellio H, Roussot N, Bertaut A, Hervieu A, Zanetta S, Tharin Z, Vincent J, Bengrine L, Hennequin A, Guion JF, Boudrant A, Collot T, Ghiringhelli F, Fumet JD. FOLFIRINOX-3 plus bevacizumab (bFOLFIRINOX3) in chemo-refractory metastatic colorectal cancer: a multicenter phase II trial. Future Oncol. 2025 Mar;21(6):699-706. doi: 10.1080/14796694.2025.2461446. Epub 2025 Feb 6.

  PMID: 39913183 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2019
• First Posted: January 7, 2019
• Study Start: November 7, 2018
• Primary Completion: January 16, 2023
• Study Completion: July 16, 2025
• Last Updated: February 17, 2025

Record last verified: 2025-02

Locations

FR (1)