NeoAdjuvant, Spare-Adjuvant (NASA) in Stage IIIB- IV (M1a) Melanoma
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 55
- Locations
- 1
- Primary Endpoint
- Overall survival
Study Overview
Brief Summary
This study evaluates the impact of neoadjuvant Programmed cell death Protein 1 (PD-1)-based treatment regimens in patients with resectable stage IIIB-M1a cutaneous or unknown primary melanoma at high risk of relapse without adjuvant therapy after definitive lymphadenectomy and irrespective of pathologic response outcome on the 2-year overall survival (OS). It was hypothesized that neoadjuvant PD1 inhibitor-based treatment without adjuvant treatment does not significantly (non-inferior) impact OS in this study patient population. Patients will be randomized to either two infusions of pembrolizumab or one infusion of ipilimumab plus nivolumab followed by a single infusion of nivolumab. Patients will undergo follow-up and restaging scans to assess event-free survival at 12 months and OS at 24 months after the first neoadjuvant treatment infusion.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent will be obtained to participate in the study, and HIPAA authorization for the release of personal health information.
- •Subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee, including randomization.
- •Age ≥ 18 years at the time of consent.
- •ECOG Performance Status of 0-
- •Histological confirmation of cutaneous melanoma or melanoma of unknown primary.
- •AJCC stage IIIB/IVa resectable disease that is measurable by iRECIST criteria.
- •Adequate hematologic, renal, hepatic, and heart function
Exclusion Criteria
- •Prior treatment with PD-1 Programmed cell death Protein 1 (PD-1) and Cytotoxic T-lymphocyte Antigen 4 (CTLA-4).
- •Has an active autoimmune disease that requires systemic treatment with the use of disease-modifying agents or immunosuppressive drugs. For corticosteroids, up to 10 mg of prednisone daily, or an equivalent dose, is permitted. Hormone replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Any condition, including laboratory abnormalities, that, in the opinion of the investigator, places the subject at unacceptable risk if he/she were to participate in the study. This includes, but is not limited to, serious medical conditions or psychiatric illnesses that are likely to interfere with participation in this clinical study.
Arms & Interventions
Arm A
Participants receive pembrolizumab 200 mg IV, every 3 weeks, times 2 infusions followed by lymph node dissection, followed by no adjuvant treatment.
Intervention: Pembrolizumab (Drug)
Arm B
Participants receive ipilimumab (3 mg/kg) plus nivolumab (1 mg/kg) x one infusion, followed by a single infusion of nivolumab 240 mg IV 3 weeks later, followed by lymph node dissection, followed by no adjuvant treatment
Intervention: Ipilimumab plus nivolumab (Drug)
Outcomes
Primary Outcomes
Overall survival
Time Frame: 2-year
The overall survival (OS) rate will be defined from the initiation of study treatments for the combined patient cohorts (cohort A and cohort B).
Secondary Outcomes
- Event - Free Survival (EFS)(1-year)
- Major pathologic response (MPR) rate(Up to 12 weeks)
- Treatment Related Adverse Events (TRAEs)(Up to 12 weeks)