iRECIST Evaluation's Relevance for DCR in MMR/MSI Metastatic Colorectal Cancer Patients on Nivolumab and Ipilimumab

NCT03350126 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: NIPICOL C17-01
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 8

Brief Summary

This is a non-randomized study, open label phase II study. The purpose of this study is to evaluate disease control rate (DCR) by RECIST and iRECIST at 12 weeks. Evaluation of RECIST and iRECIST will be done in each center in order to choose the optimal therapy (Assessment by Investigators). A centralized evaluation of RECIST and iRECIST, will be organized in Saint-Antoine.

Conditions

Metastatic Cancer Colorectal

Keywords

MSI or MMR

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate (DCR)

  According with RECIST 1.1 and iRECIST

  At 12 weeks

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  PFS is defined as time from date of first dose of study treatment to date of first Progression (accordance with RECIST 1.1 or iRECIST) or death due to any cause - Up to 24 months

• Overall Response Rate (ORR)

  Up to 24 months

• Overall Survival (OS)

  Up to 24 months

• Toxicity according to NCI-CTCAE version 4.0 (National Cancer Institute Common Terminology Criteria for Adverse Events),

  Up to 24 months

Study Arms (1)

Experimental arm

EXPERIMENTAL

Therapy induction (12 weeks) Nivolumab (IV) and Ipilimumab (IV) - every 21 days - 4 cycles Then Nivolumab (IV) alone every 15 days - 20 cycles - until 12 months

Drug: Ipilimumab 200 MG in 40 ML Injection; Drug: Nivolumab 10 MG/ML

Interventions

Ipilimumab 200 MG in 40 ML Injection DRUG

Induction therapy (12 weeks): Nivolumab 3mg/kg intravenously (IV) over 60 minutes and Ipilimumab 1mg/kg (IV) over 90 minutes Q3W

Experimental arm

Nivolumab 10 MG/ML DRUG

Induction therapy (12 weeks) : Nivolumab 3mg/kg intravenously (IV) over 60 minutes and Ipilimumab 1mg/kg (IV) over 90 minutes Q3W Maintenance therapy (40 weeks): Nivolumab monotherapy IV over 60 minutes Q2W until iRECIST progression or if no PD for one year.

Experimental arm

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent,
• For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study drug,
• Men and women are required to use adequate birth control during the study (when applicable):
• Within the frame of this study, female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control (i.e., pregnancy rate of less than 1% per year) during the period of treatment and for 5 months for women and 7 months for men from the last treatment administration. Men must refrain from donating sperm during this same period.
• Contraceptive methods that result in a low failure rate when used consistently and correctly include methods such as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), some intrauterine devices, intrauterine hormone-releasing stem, true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant), bilateral tubal occlusion, or a female partner who is not of childbearing potential or a male partner who has had a vasectomy. Women and female partners using hormonal contraceptive must also use a barrier method i.e. condom or occlusive cap (diaphragm or cervical/vault caps).
• A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\>12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
• Histologically proven metastatic adenocarcinoma of the colon and/or rectum,
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study,
• dMMR DNA (protein expression by ICH and/or MSI by PCR):
• Tumor MMR and/or MSI will be assessed per local guidelines: ICH with two (anti-MLH1 and anti-MSH2) or four antibodies (anti-MLH1, anti-MSH2, anti-MSH6 and anti-PMS2) and/or PCR (with PROMEGA: BAT25, BAT26, NR21, NR24, NR27\]) by the investigators prior to screening,
• Age ≥18 years,
• The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1,
• Progression during, after, or who are intolerant or have contraindication to approved standard therapies for the metastatic disease which must include at least:
• Fluoropyrimidine, and oxaliplatin and irinotecan.
• Anti-EGFR therapy if wild-type RAS and RAF and anti-VEGF therapy,

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
• Unresolved toxicity higher than Grade 1, NCI-CTCAE v 4.03, attributed to any prior therapy
• Treatment with any investigational medicinal product within 28 days prior to study entry,
• Major surgical procedure within 4 weeks prior to initiation of study treatment,
• Other serious and uncontrolled non-malignant disease (including active infection),
• Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for \>5 years,
• Pregnant or breastfeeding women,
• History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, Note: History of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
• Note: Controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest imaging,
• Human immunodeficiency virus (HIV),
• Active hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen \[HBsAg\] test prior to randomization) or hepatitis C virus (HCV), Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible.
• Note: Patients positive for HCV antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid (RNA).
• Administration of a live, attenuated vaccine within four weeks prior to start of treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study,

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead
• Bristol-Myers Squibb: collaborator

Study Sites (8)

Institut Sainte Catherine

Avignon, France

Location

CHRU Besançon

Besançon, France

Location

Henri Mondor Hospital

Créteil, France

Location

IHFB

Levallois-Perret, France

Location

Centre Leon Berard

Lyon, France

Location

CHU Nantes - Hôtel Dieu

Nantes, France

Location

Hospital Saint Antoine

Paris, 75012, France

Location

CHU Poitiers

Poitiers, France

Location

Related Publications (4)

• Depotte L, Nay P, Borg C, Meurisse A, Henriques J, Bennouna J, De La Fouchardiere C, Tougeron D, Mazard T, Chibaudel B, Tournigand C, Vernerey D, Pigneur F, Andre T, Cohen R. Interplay between sarcopenia, GDF-15, and the efficacy of nivolumab plus ipilimumab in patients with mismatch repair deficient metastatic colorectal cancer: final survival analysis of the phase II GERCOR NIPICOL study. J Immunother Cancer. 2025 May 19;13(5):e011220. doi: 10.1136/jitc-2024-011220.

  PMID: 40389373 DERIVED

• Ratovomanana T, Nicolle R, Cohen R, Diehl A, Siret A, Letourneur Q, Buhard O, Perrier A, Guillerm E, Coulet F, Cervera P, Benusiglio P, Labreche K, Colle R, Collura A, Despras E, Le Rouzic P, Renaud F, Cros J, Alentorn A, Touat M, Ayadi M, Bourgoin P, Prunier C, Tournigand C, Fouchardiere C, Tougeron D, Jonchere V, Bennouna J, de Reynies A, Flejou JF, Svrcek M, Andre T, Duval A. Prediction of response to immune checkpoint blockade in patients with metastatic colorectal cancer with microsatellite instability. Ann Oncol. 2023 Aug;34(8):703-713. doi: 10.1016/j.annonc.2023.05.010. Epub 2023 Jun 1.

  PMID: 37269904 DERIVED

• Ratovomanana T, Cohen R, Svrcek M, Renaud F, Cervera P, Siret A, Letourneur Q, Buhard O, Bourgoin P, Guillerm E, Dorard C, Nicolle R, Ayadi M, Touat M, Bielle F, Sanson M, Le Rouzic P, Buisine MP, Piessen G, Collura A, Flejou JF, de Reynies A, Coulet F, Ghiringhelli F, Andre T, Jonchere V, Duval A. Performance of Next-Generation Sequencing for the Detection of Microsatellite Instability in Colorectal Cancer With Deficient DNA Mismatch Repair. Gastroenterology. 2021 Sep;161(3):814-826.e7. doi: 10.1053/j.gastro.2021.05.007. Epub 2021 May 13.

  PMID: 33992635 DERIVED

• Cohen R, Bennouna J, Meurisse A, Tournigand C, De La Fouchardiere C, Tougeron D, Borg C, Mazard T, Chibaudel B, Garcia-Larnicol ML, Svrcek M, Vernerey D, Menu Y, Andre T. RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study. J Immunother Cancer. 2020 Nov;8(2):e001499. doi: 10.1136/jitc-2020-001499.

  PMID: 33148693 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms; Microsatellite Instability

Interventions

Ipilimumab; Injections; Nivolumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Thierry ANDRE, MD

  Hopital Saint Antoine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 22, 2017
• Study Start: December 4, 2017
• Primary Completion: January 10, 2020
• Study Completion: December 1, 2025
• Last Updated: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)