Status and phase
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This study is a phase I/II, multicenter, open-label study starting with a phase I part followed by a Phase II part.
The phase I part of the study aims at evaluating the safety and efficacy (in terms of abscopal effect at week 6) of the treatment combination schema of Stereotactic Body Radiation Therapy (SBRT) and PD-1 plus CTLA-4 inhibitors in patients with metastatic melanoma. Patients will be assigned in one of 3 cohorts depending the metastatic site. 18 patients will be enrolled in each cohort.
Once the recommended optimal radiotherapy dose has been declared for the 3 cohorts, patients will be enrolled in the phase II part of the study in order to evaluate the activity (progression-free survival at 6 months) of SBRT given in combination with immune checkpoints inhibitors in patients with metastatic melanoma.
66 patients will be included in the phase II.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Patients with histologically-proven metastatic and/or unresectable melanoma (stage IIIc-IV, M1a-c as per AJCC 8th Edition), including mucosal melanoma, without evidence of active intra-cranial disease.
Patients with tumor PD-L1 expression <1%.
Patients are included regardless of BRAFV600 mutation status. BRAFV600 mutation status must be documented.
Patients with a metastatic lesion located on liver, lung, or bone and eligible for a SBRT.
Patients should present at least two lesions: one lesion to be irradiated and one distant lesion that will serve as control. Lesion to be irradiated will be selected on the basis of symptomatology, safety and/or location. Preferentially, both lesions should be measurable per RECIST 1.1. If only the control lesion is measurable but not the irradiated lesion, eligibility will be discussed with the sponsor.
Age ≥18 years at the time of study entry.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
Life expectancy of at least 3 months.
Patients able to participate and willing to give informed consent prior to performance of any study-related procedures and to comply with the study protocol.
Screening laboratory values must meet the following criteria and should be obtained prior to commencement of treatment:
Adequate cardiac and respiratory functions defined as New York Heart Association (NYHA) class 1 and SaO2 > 90%.
Patient must be naïve to systemic treatment for locally advanced and/or metastatic disease (i.e., no prior systemic anticancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant therapies (including Interferon α and Ipilimumab) is permitted if it was completed at least 12 weeks before start of treatment and all related AEs have either returned to baseline or stabilized.
Prior radiotherapy or radiosurgery must have been completed at least 4 weeks prior to the first dose of the study treatment.
Women of childbearing potential (WOCBP) must use two appropriate methods of contraception to avoid pregnancy for 23 weeks (30 days plus the time required for Nivolumab/Ipilimumab to undergo five half-lives) after the last dose of investigational drug.
Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
Men who are sexually active with WOCBP must use two contraceptive methods including at least one method with a failure rate of less than 1% per year for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception
Absence of any psychological, familial, sociological or geographical condition that potentially hampers compliance with the study protocol and follow-up after treatment discontinuation schedule.
Patient affiliated to a Social Health Insurance in France.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
6 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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