Melanoma stage IIIB/C
Conditions
Interventions
Trade Name: OPDIVO
Product Name: Nivolumab
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Nivolumab
Other descriptive name: NIVOLUMAB
Concentration unit: mg/ml milligram(s)/millilitr
Sponsors
Hôpitaux Universitaires de Strasbourg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject over 18 years old with stage IIIB/IIIC melanoma with lymph node metastases, with at least one =1 cm3 that is accessible to cryotherapy under interventional radiology (IR), assessed at the inclusion visit (V1). 2. ECOG performance status (0 to 2) at the selection visit (V0) 3. Woman or man of reproductive age with no desire to procreate for the duration of their participation in the study, agreeing to use dual-method contraception, with at least one barrier method, and for 5 months after the final infusion of Nivolumab for women and 7 months for men 4. Leukocytes >2000/mm3, neutrophils >1500/mm3, platelets >100,000/mm3, haemoglobin >9g/dl at the selection visit (V0) 5. Total bilirubin 40 ml/min (using the Cockcroft-Gault equation) at the selection visit (V0) 8. Patient is covered by a medical insurance scheme 9. Patient able to read and speak French, and to sign and date an informed consent form for the study, including the translational research 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 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 10. Pregnancy (women of childbearing potential : positive blood pregnancy test at the selection visit (V0) ) andor breastfeeding 11. Subject under guardianship 12. History of hypersensitivity to ipilimumab, nivolumab or one of the excipients 13. History of severe hypersensitivity to a monoclonal antibody 14. History of positive tests for HIV or Acquired Immunodeficiency Syndrome (HIV assessed at the selection visit (V0)) 15. Positive tests for HCV or HBV indicating an acute or chronic infection at the selection visit (V0) 16. Patient presenting with an active, known or suspected autoimmune disease. The following, however, may participate: - patient with type 1 diabetes or hypothyroidism requiring substitute hormone therapy only; - patient with psoriasis, vitiligo or alopecia; - patient with conditions that are not known to reoccur without an exogenous triggering agent. 17. History of active neoplasia during the last 3 years with the exception of localised curable cancers considered to be cured, such as basal or squamous cell carcinomas, superficial bladder cancer and prostate, colon or breast carcinoma in situ. 18. Active systemic infection 19. Patient with a condition requiring systemic steroid treatment (at a dose >10 mg/prednisone equivalent or at unstable dose) or another immunosuppressant within/following 14 days of study drugs administration. Inhaled steroids and treatment for adrenal insufficiency, however, are permitted. 20. Contraindication for the cryotherapy procedure as assessed by the radiologist (due to tumour size or proximity to a vascular or nerve structure giving the procedure an unacceptable level of risk) at the inclusion visit (V1) 21. Clotting disorder that may interfere with the cryoablation, assessed at the selection visit (V0) 22. Contraindication for MRI with gadolinium-based contrast media 23. History of uveal melanoma 24. Patient having received prior treatment for their melanoma, in particular, patient previously treated with interferon fewer than 3 months ago or with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD-137 or anti-CTLA-4 antibody. Patients who have undergone primary melanoma surgery and the excision of in-transit metastases, as well as adjuvant therapy with interferon if completed over 3 months ago are eligible. 25. Contraindication for general and/or local anaesthesia 26. Patient operated on under general anaesthesia, within the 4 weeks prior to the planned Nivolumab infusion. 27. Patient operated on epidural anaesthesia, within the 72 h prior to the planned Nivolumab infusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Pilot study for the targeted destruction of melanoma metastases by an infusion of nivolumab, cryotherapy using interventional radiology (IR) combined with in situ anti-cancer immunotherapy with ipilimumab. ;Secondary Objective: 1)Impact on target and non-targeted lesions 2)Any impact on progression-free and overall survival (long-term follow-up of this cohort vs recent control cohort ([patients with stage IIIB melanoma treated 1 year earlier]) 3) To assess the safety of the combination (IV nivolumab + cryotherapy + intratumoural ipilimumab) ;Primary end point(s): Number of failures linked to the procedure, from all causes (unless the patient changes his/her mind = withdrawal from the study). In the context of this study, failure is defined as follows: . Technically impossible to perform the cryoablation procedure, or . Impossible to inject at least 2 ml of ipilimumab into the treated lymphadenopathy. ;Timepoint(s) of evaluation of this end point: Visit 4 (after ipilimumab injection) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Comparison of the size of target and non-targeted lymphadenopathies before and 4 to 6 weeks after the procedure. 2) Comparison of overall and progression-free survival of this cohort with a recent historical cohort (similar patients at stages IIIB/C treated in the dermatology clinic 1 year earlier). 3) Analysis of adverse events and serious adverse events;Timepoint(s) of evaluation of this end point: 1/ Visit 1 and Visit 5 2/Last patient last visit 3/Last patient last visit | — |
Countries
France
Contacts
Public ContactArmelle DREXLER
Direction de la recherche clinique et des Innovations
Outcome results
None listed