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Clinical Trial NCT06715241 (COLIBRI-2) for LOCALLY ADVANCED CERVICAL CANCERS is active, not recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here. | ||
A MULTICENTER, SEEKING SIGNAL, RANDOMISED, OPEN-LABEL PHASE II OF RELATLIMAB AND NIVOLUMAB VS NIVOLUMAB ALONE IN LOCALLY ADVANCED CERVICAL CANCERS (COLIBRI-2) Phase 2 77 Randomized Open-Label
Primary Objective
* To evaluate the clinical activity of relatlimab and nivolumab induction treatment before standard CCRT in locally advanced cervical cancer
Secondary Objectives
- To further document the clinical activity of relatlimab and nivolumab
- To document the safety of the proposed combination in the target population
Exploratory Objectives
- To identify candidate biomarkers that may correlate with li...
A MULTICENTER, SEEKING SIGNAL, RANDOMISED, OPEN-LABEL PHASE II OF RELATLIMAB AND NIVOLUMAB VS NIVOLUMAB ALONE IN LOCALLY ADVANCED CERVICAL CANCERS
- COLIBRI-2
- GINECO-CE111b
- 2024-514032-25-00 (EU Study (CTIS) Number)
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ExperimentalArm A: Nivolumab and relatlimab | combination of relatlimab and nivolumab wich are two immunotherapy treatments Induction: Nivolumab 360 mg/relatlimab 360 mg fixed dose combination, IV, 6 weeks Off treatment period: 4 to 6 weeks Maintenance: Nivolumab 480 mg/relatlimab 480 mg fixed dose combination, IV 13 cycles (Q4W): 52 weeks |
OtherArm B: Nivolumab only | Nivolumab alone Induction: Nivolumab alone 360 mg, IV2 cycles (Q3W): 6 weeks Off treatment period: 4 to 6 weeks Maintenance: Nivolumab alone 480 mg, IV, 13 cycles (Q4W): 52 weeks |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Primary outcome | Objective response rate at the end of the 6-week induction period is defined as the rate of patients with CR or PR as per RECIST V1.1 at the end of the induction period.
Response will be assessed according to RECIST v1.1 criteria as per investigator assessment.
ORR-6w will be derived as a binary variable (success/failure), based on the following rules:
* Patients showing an objective response based on RECIST tumoral evaluation performed at the end of the induction period will be considered in " success ".
* Patients showing a progressive disease based on RECIST tumoral evaluation performed at the end of the induction period will be considered in " failure ".
* Patients with no tumoral evaluation at the end of the induction period and with early death or clinical progression or treatment discontinuation due to toxicity will be considered in " failure ".
* Patients who do not meet any of the conditions above will be consider as " non evaluable " for the primary endpoint. | From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Progression Free survival (PFS) | PFS is defined as the time from randomization until the date of event defined as the first objective documented progression, according to investigator assessment of RECIST v1.1 or death (by any cause in the absence of progression). Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST assessment. | From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days |
Time to local progression (TTlP) | TTlP will be measured from the date of randomization to the date of event defined as the 1st local progression, and censored at the date of last tumor assessment for patients without event at the time of the analysis. | From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days |
Time to metastatic progression (TTmP) | TTmP will be measured from the date of randomization to the date of event defined as the 1st metastatic progression, and censored at the date of last tumor assessment for patients without event at the time of the analysis. Patients with no post-baseline tumoral evaluation (e.g withdrawal of consent) will be censored at day 1 for the evaluation of PFS, TTlP and TTmP. | From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days |
Overall Survival (OS) | OS isis defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. | From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days |
ORR after CCRT/at the end of the maintenance period | It is defined as the rate of patients with CR or PR as per RECIST V1.1 after CCRT/at the end of the maintenance period. ORR after CCRT/ at the end of the maintenance period will be derived in the same way as ORR-6w. | From the date of randomization until patients operated with late complete debulking surgery, assessed up 100 days |
Female patients aged ≥18 years at time of inform consent signature.
Patients must have histologically confirmed diagnosis of cervical squamous or adenosquamous carcinoma stage IIB to IVA according to FIGO 2018 (Appendix 1) and no evidence of metastatic disease (M0). Note: Nodal staging may be either surgical or by imaging (MRI/PET-CT) with pathological lymph node size defined by a short-axis diameter of ≥10mm (axial plane) or FDG uptake greater than that of the surrounding tissue and corresponding to the LN structure on CT when CT was performed for PETCT analysis.
Patients must be naïve from prior anti-cancer treatment (all type) and eligible to standard CCRT as per standard practice and investigator' judgement.
Known HPV status as per local assessment.
Patient accepting to undergo a new cervix biopsy and with at least one lesion with a diameter ≥10 mm, visible by medical imaging and accessible to percutaneous sampling (needle biopsies 16 gauge or larger) that permit core needle biopsy (ideally 4 cores) without unacceptable risk of a major procedural complication.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 2).
Adequate organ and marrow function with following lab values within 7 days before C1D1:
- Absolute neutrophil count (ANC) ≥1500/μL
- White blood cell (WBC) >3000/μL
- Platelets ≥100 000/μL
- Hemoglobin (Hb) ≥9 g/dL
- Total bilirubin ≤1.5× upper limit of normal (ULN) unless due to Gilbert's syndrome
- ASAT /ALAT ≤3 ULN
- Creatinine ≤1.5 within normal limit, or
- Creatinine clearance ≥ 40 mL/min according to CKD-EPI formula (Appendix 3)
- Troponin T or I < 2 x ULN
Adequate cardiovascular function documented by:
- QTc interval <450 msec.
- Left ventricular Ejection fraction > 50% based on screening echocardiogram (ECHO) or multigated acquisition scan (MUGA).
- Controlled blood pressure (BP, <150/90mmHg), with or without current antihypertensive treatment.
- No congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades de pointes).
- No stroke (including transient ischemic attack \[TIA\]), myocardial infarction, or other clinically significant ischemic event within 12 months before first dose.
- No prior history of myocarditis.
Women of childbearing potential
- must have a negative serum pregnancy test within 7 days prior C1D1 and use adequate contraceptive methods (for example, intrauterine device \[IUD\], birth control pills unless clinically contraindicated, or barrier device - see Appendix 4) beginning 2 weeks before the first dose of study drugs and for up to 6 months after the final dose of study drugs (i.e., 30 days \[duration of ovulatory cycle\] plus the time required for relatlimab and nivolumab to undergo approximately five halflives).
- 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, fallopian tubes, and/or uterus).
Ability to understand and sign informed consent and willingness to comply with the study procedures before study entry.
Covered by a medical insurance.
Evidence or treatment for another malignancy within 3 years prior to study entry. Curatively treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia is allowed.
History of severe allergic or other hypersensitivity reactions to:
- chimeric or humanized antibodies or fusion proteins,
- biopharmaceuticals produced in Chinese hamster ovary cells, or
- any component of the study treatments formulation.
Patients with:
- Active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) unless their HBV is stably controlled on nucleoside analogs (eg entecavir or tenofovir) which will be continued for the duration of the study. Note: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. HBV DNA test must be performed in these patients prior to C1D1.
- Active hepatitis C. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA, or
- HIV infection. Patients with prior organ or bone marrow transplant.
Patients with active, suspected or 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, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 5 for a more comprehensive list of pre-existing autoimmune diseases and immune deficiencies) with the following exceptions:
patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone,
patients with controlled Type 1 diabetes mellitus,
patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
- rash must cover less than 10% of body surface area (BSA).
- disease is well controlled at baseline and only requiring low potency topical steroids.
- no acute exacerbations of underlying condition within the previous 12 months requiring PUVA \[psoralen plus ultraviolet A radiation\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids.
Patients not respecting the minimal washout period or anticipation of need during the study of the following medications:
For "Systemic immunosuppressive medication (e.g.corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents)", a minimal wash out period before C1D1 ≥ 2 weeks is requested.
But use during the study is not allowed with the exceptions of intranasal, inhaled, or topical corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10mg/day of prednisone, or an equivalent corticosteroid.
For "Systemic immunostimulatory (e.g., interferons and IL-2), a minimal wash out period ≥ 4 weeks or 5 * t(1/2) of medication whichever is longer.
But use during the study is not allowed.
- Patients with any serious or uncontrolled medical disorder that, in the opinion of the investigator, may have increased the risk associated with trial participation or trial treatment administration, impaired the ability of the patients to receive protocol therapy, or interfered with the interpretation of trial results.
- Patients have received a live/attenuated vaccine within 30 days of C1D1 (inactivated vaccines were permitted).
- Pregnant or lactating women.
- Patients deprived of liberty, under guardianship, or under curatorship.
ARCAGY/ GINECO GROUP