NeoAdjuvant, Spare-Adjuvant (NASA) in Stage IIIB-IV (M1a) Melanoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUNC Lineberger Comprehensive Cancer Center
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 0-2.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Pembrolizumab
DrugPembrolizumab 200 mg IV, every 3 weeks
Ipilimumab plus nivolumab
DrugSingle infusion of concurrent ipilimumab (3 mg/kg) plus nivolumab (1 mg/kg) followed by a single infusion of nivolumab 240 mg IV 3 weeks later
Treatment groups
55 Participants
are divided into 2 treatment groupsGroup A: Arm AExperimental treatment 1 intervention
Group B: Arm BExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Overall survival
The overall survival (OS) rate will be defined from the initiation of study treatments for the combined patient cohorts (cohort A and cohort B).
Time frame
2-yearSecondary outcomes
1
Event - Free Survival (EFS)
The Event - Free Survival (EFS) rate will be defined from the initiation of study treatments for the combined patient cohorts (cohort A and cohort B).
Time frame
1-year2
Major pathologic response (MPR) rate
The MPR rate for each of the two study treatment cohorts (cohort A and cohort B) will be defined using established pathologic response criteria. Pathologic response will be assessed by determining the percentage of residual viable tumor in the resected specimen. Major pathologic response is defined as ≤10% residual viable tumor, and pathologic complete response is defined as the absence of viable tumor cells.
Time frame
Up to 12 weeks3
Treatment Related Adverse Events (TRAEs)
TRAEs are defined as adverse events assessed by the investigator as related to study treatment, Grade 3 or higher grades. The incidence of TRAEs will be determined separately for each of the two cohorts and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 6.0. CTCAE classifies severity as follows: Grade 1 - asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 - minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 - severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 - life-threatening consequences; urgent intervention indicated. Grade 5 - death related to the adverse event.
Time frame
Up to 12 weeksSponsors and contacts
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Source ClinicalTrials.gov