Phase II Study on NIVolumab in combination with FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan)/Bevacizumab in first line chemotherapy of Advanced COloRectal cancer patients with mutated RAS or BRAF genes.

Phase 1

• Conditions: Advanced colorectal cancer; MedDRA version: 21.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002893-38-IT
• Lead Sponsor: GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-04
• Last Update Posted: 9 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

•Age = 18 years on day of signing informed consent.
•Histologically confirmed metastatic CRC RAS/BRAF mutated.
•Suitable for first line chemotherapy.
•Life expectancy > 3 months.
•At least one site of measurable disease per RECIST criteria.
•Performance status of 0-1 on the ECOG Performance Scale.
•Adequate organ function, all screening labs should be performed within 28 days of treatment initiation.
•Availability of 1 tumor block at baseline.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

•Prior chemotherapy.
•Systemic corticosteroids within 2 weeks of the first dose of nivolumab.
•Diagnosis of immunodeficiency or patient who is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment.
•Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
•Active and untreated brain (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are not using steroids for at least 7 days prior to trial treatment.
•Evidence of interstitial lung disease, active non-infectious pneumonitis, or a history of grade 3 or greater pneumonitis.
•Active infection requiring systemic therapy.
•History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
•Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
•Live vaccine within 30 days prior to the first dose of trial treatment.
•Women with a positive pregnancy test at enrollment or prior to administration of study medication.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To evaluate the efficacy and safety of the combined treatment, the time of progression and the duration of the treatment response and the quality of life of the patients.<br>To evaluate the Tumor Mutation Burden , MSI status and the role of genetic and molecular pattern with patient’s outcome.;Main Objective: Evaluate the activity of Nivolumab in combination with FOLFOXIRI and bevacizumab.;Primary end point(s): To demonstrate that adding nivolumab to standard colorectal first line chemotherapy improves the Overall Response Rate as determinated by investigators using RECIST 1.1 criteria.;Timepoint(s) of evaluation of this end point: From the start of the study treatment until the end of treatment.