Informations générales (source: ClinicalTrials.gov)
A MULTICENTER, SEEKING SIGNAL, RANDOMISED, OPEN-LABEL PHASE II OF RELATLIMAB AND NIVOLUMAB VS NIVOLUMAB ALONE IN LOCALLY ADVANCED CERVICAL CANCERS (COLIBRI-2)
Interventional
Phase 2
ARCAGY/ GINECO GROUP (Voir sur ClinicalTrials)
décembre 2024
décembre 2030
13 juin 2025
Multicenter, open-label, randomized, seeking signal (non-comparative), Phase II aiming to
assess the clinical activity of the combination relatlimab + nivolumab in locally
advanced cervical cancer eligible to standard CCRT
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CHI DE CRETEIL | Jean-David FUMET | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT CURIE | Hélène SALAUN | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Alexandra LEARY | Contact (sur clinicalTrials) | |||
| GRPE HOSP DIACONESSES-CROIX ST-SIMON | Antoine ANGELERGUES | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine Lacassagne - 06189 - Nice - France | Philippe FOLLANA | Contact (sur clinicalTrials) | |||
| Centre CARIO - HPCA - 22190 - Plerin - France | Anne-Claire HARDY-BESSARD | Contact (sur clinicalTrials) | |||
| Centre Eugène Marquis - 35042 - Rennes - France | Thibault DE LA MOTTE ROUGE | Contact (sur clinicalTrials) | |||
| Centre François Baclesse - 14076 - Caen - France | Florence JOLY | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Lyon Sud - Pierre-benite - France | Gilles FREYER | Contact (sur clinicalTrials) | |||
| Centre Jean Perrin - Clermont-ferrand - France | Elsa KALBACHER | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - 69373 - Lyon - France | Isabelle RAY-COQUARD | Contact (sur clinicalTrials) | |||
| Centre Oscar Lambret - Lille - France | Abel CORDOBA | Contact (sur clinicalTrials) | |||
| CHRU Besançon - Hôpital Jean Minjoz - 25030 - Besancon - France | Laura MANSI | Contact (sur clinicalTrials) | |||
| CHRU de Tours - Hôpital Bretonneau - Centre Henry Kaplan - 37044 - Tours - France | Contact (sur clinicalTrials) | ||||
| CHRU Lille - Hôpital Jeanne de Flandre - 59000 - Lille - France | Yohan KERBAGE | Contact (sur clinicalTrials) | |||
| CHU de BREST - Hôpital Cavale Blanche - 29200 - Brest - France | Laura DEIANA | Contact (sur clinicalTrials) | |||
| CHU de Dijon - 21079 - Dijon - France | Marie CHAIX | Contact (sur clinicalTrials) | |||
| CHU de Limoges - Hôpital Dupuytren - 87042 - Limoges - France | Elise DELUCHE | Contact (sur clinicalTrials) | |||
| CHU de Poitiers - Hôpital de la Milétrie - 86021 - Poitiers - France | Sheik EMAMBUX | Contact (sur clinicalTrials) | |||
| CHU Saint-Etienne - Pôle de Cancérologie - 42271 - Saint-etienne - France | Gilles FREYER | Contact (sur clinicalTrials) | |||
| ICANS - Institut de cancérologie Strasbourg Europe - 67200 - Strasbourg - France | Lauriane EBERST | Contact (sur clinicalTrials) | |||
| ICL - Centre Alexis Vautrin - 54519 - Vandoeuvre-les-nancy - France | Marie-Christine KAMINSKY | Contact (sur clinicalTrials) | |||
| ICM Val d'Aurelle - 34298 - Montpellier - France | Contact (sur clinicalTrials) | ||||
| ICO - Centre René Gauducheau - 44805 - Saint-herblain - France | Dominique BERTON | Contact (sur clinicalTrials) | |||
| ICO Paul Papin - 49055 - Angers - France | Paule AUGEREAU | Contact (sur clinicalTrials) | |||
| Institut Bergonié - 33076 - Bordeaux - France | Adeline PETIT | Contact (sur clinicalTrials) | |||
| Institut Paoli Calmettes - 13273 - Marseille - France | Renaud SABATIER | Contact (sur clinicalTrials) | |||
| Oncopole Claudius Regaud - 31059 - Toulouse - France | Sarah BETRIAN-LAGARDE | Contact (sur clinicalTrials) | |||
| Recherche Oncologique Clinique 37 (ROC 37) - 37170 - Tours - France | Pierre COMBE | Contact (sur clinicalTrials) | |||
| Sainte-Catherine Institut du Cancer Avignon-Provence - 84918 - Avignon - France | Bertrand BILLEMONT | Contact (sur clinicalTrials) | |||
Critères
Femme
Inclusion Criteria:
- 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.
- 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:
1. 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.
2. 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.