Analysis of the efficacy and safety of two combination treatment regimens of nivolumab and ipilimumab in patients with dMMR and / or MSI metastatic colorectal cancer: A GERCOR open-label, randomized, non-comparative, two-stage phase II trial (NIPISAFE)

Association Gercor19 sites in 1 country93 target enrollmentJanuary 9, 2025

DrugsBMS936558 IBI310 OPDIVO 10 mg/mL concentrate for solution for infusion.ABP 206 BMS734016 HLX13 YERVOY 5 mg/ml concentrate for solution for infusion

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Not specified
Sponsor: Association Gercor
Enrollment: 93
Locations: 19
Primary Endpoint: The co-primary endpoint of this study is Grade 3 or 4 TRAEs during the first 24 weeks (NCI CTCAE v5.0) and PFS at week 24
Status: Not yet recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

To assess the safety (grade 3 or 4 TRAEs) profile according to NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 of two different combination schemes of nivolumab plus ipilimumab during the first 24 weeks of treatment,
To assess PFS at week 24 for two combination schemes.

Registry

euclinicaltrials.eu

Start Date

January 9, 2025

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Association Gercor

Responsible Party

Principal Investigator

Dr GARCIA-LARNICOL

Scientific

Association Gercor

Eligibility Criteria

Inclusion Criteria

•Signed and dated patient informed consent form (ICF) and willingness to comply with all study procedures and availability for the study duration
•Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 7 days prior to initiation of study treatment: - Hematological status: White blood cell > 2000/μL; o Neutrophils > 1500/μL; o Platelets > 100.000/μL; o Hemoglobin > 9.0 g/dL; - Adequate renal function: o Serum creatinine level < 150 μM; - Adequate liver function: o Serum bilirubin ≤ 1.5 x upper normal limit (ULN); o Alkaline phosphatase (ALP) ≤ 3 x ULN; o Alanine aminotransferase (ALT) ≤ 3.0 x ULN; o Aspartame aminotransferase (AST) ≤ 3.0 x ULN; o Prothrombin time (PT)/International normalized ratio (INR) and partial PT (PTT) ≤ 1.5 x ULN unless participants are receiving anticoagulant therapy and their INR is stable and within the recommended range for the desired level of anticoagulation,
•Females of childbearing potential must have negative urine or serum pregnancy test within 7 days before starting study treatment,
•Women of childbearing potential should use effective contraception during treatment and 5 months thereafter. Males should use condoms during treatment and 7 months thereafter,
•Registration in a national health care system (Protection Universelle Maladie [PUMa] included)
•Age ≥ 18 years
•ECOG PS of 0, 1, or 2
•Histologically or cytologically confirmed colorectal adenocarcinoma
•Documented advanced or metastatic disease not suitable for complete surgical resection
•At least one measurable lesion as assessed by CT-scan or magnetic resonance imaging (MRI) according to RECIST v1.1 and feasibility of repeated radiological assessments. Participants with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately

Exclusion Criteria

•Known brain metastases or leptomeningeal metastases
•Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease
•Prior malignancy active within the previous 3 years except for: - Locally curable cancers that have been apparently cured (e.g. squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast); - Lynch syndrome-related non-colorectal cancer in complete remission for > 1 year
•Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test prior to randomization) virus (HBV) or hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. 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. Patients positive for HCV antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid.
•Prior allogeneic bone marrow transplantation or prior solid organ transplantation
•Any serious or uncontrolled medical disorder that, in the opinion of Investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results
•Known allergy/hypersensitivity to any component of study agents
•Administration of a (attenuated) live vaccine within 28 days of planned start of study therapy of known need for this vaccine during treatment
•Patient on tutelage or guardianship or under the protection of justice.
•Persistence of toxicities related to prior chemotherapies grade > 1 (NCI CTCAE v5.0; except alopecia, fatigue, or peripheral sensory neuropathy, which can be grade 2)

Outcomes

Primary Outcomes

The co-primary endpoint of this study is Grade 3 or 4 TRAEs during the first 24 weeks (NCI CTCAE v5.0) and PFS at week 24

Secondary Outcomes

PFS and ORR at weeks 24 and 48, and at 2 years (iRECIST)
OS at weeks 24 and 48, and at 2 years
AEs (NCI CTCAE v5.0)
Treatment and iAEs
Percentage of patients who received immune modulating concomitant medication (e.g., corticosteroids, infliximab, mycophenolate mofetil)
Percentage of patients who received hormonal replacement therapy for immune-related endocrine toxicities
Median time to onset, median time to resolution of SAEs and TRAEs (grade 3-4)
Score changes in EORTC QLQ-C30 and NCI-PRO-CTCAE scales
ORR at weeks 24 and 48, and at 2 years (RECIST v1.1)
PFS at week 48 and at 2 years (RECIST v1.1)