Neoadjuvant Pembrolizumab in Patients With Stage IIb/c Melanoma

Official title

Neoadjuvant Pembrolizumab in Patients With Stage IIb/c Melanoma, a Phase II Double-blind Placebo-controlled Randomized Trial

Overview

A phase II double-blind placebo-controlled randomized trial. Patients with a clinical suspicion of a thick primary melanoma without clinical suspicion or evidence of lymph-node engagement will undergo a 3 mm punch biopsy to verify the diagnosis and ascertain eligibility. Patients will receive 1 cycle of pembrolizumab 400 mg or placebo and 4 weeks later undergo a wide local excision and sentinel lymph node biopsy according to the national guideline recommendations . The primary objective is to evaluate the pathological response of one cycle of neoadjuvant pembrolizumab in patients with biopsy-proven stage IIb/c melanoma. Secondary objectives include efficacy and safety analysis, as well as biomarker discovery.

Interventions

• Drug Pembrolizumab
  Immunotherapy
• Drug Placebo
  Placebo

Primary outcome measures

• Pathological response rate [Time frame: 48 month]

Secondary outcome measures (10)

• Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) [Time frame: 48 month]
• Feasibility of neoadjuvant therapy in stage II melanoma [Time frame: 48 month]
• Sentinel lymph node positivity rate [Time frame: 48 month]
• Local recurrence rate [Time frame: 48 month]
• Regional recurrence rate [Time frame: 48 month]
• Event free survival (EFS) [Time frame: 48 month]
• To assess recurrence free survival (RFS). [Time frame: 48 month]
• Distant metastasis-free survival (DMFS) [Time frame: 48 month]
• Melanoma specific survival (MSS) [Time frame: 48 month]
• Overall survival (OS) [Time frame: 48 month]

Eligibility criteria

Inclusion criteria

• Patient is ≥18 years.
• Signed informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Histopathologically confirmed primary cutaneous melanoma stage IIb/c (Breslow >2.0 mm with ulceration OR Breslow >4.0mm without ulceration) with a minimum diameter of 5 mm not completely removed by the diagnostic biopsy
• Patient planned for wide local excision and sentinel lymph node biopsy
• Adequate organ function on blood test
• Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female patients of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 150 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 150 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion criteria

• Life expectancy of less than 3 years.
• Patients who are unable to undergo general anesthesia for any reason.
• Clinical or radiographic evidence of nodal, satellite, in-transit or distant metastases
• Risk for developing in-operable disease due to study procedures as judged by study investigator
• Prior immunotherapy for any malignancy
• Use of live vaccines four weeks before or after the last study treatment.
• History of severe reactions to monoclonal antibodies.
• Active autoimmune disease or a documented history of autoimmune disease requiring systemic immunomodulatory treatment. Diabetes, rheumatoid arthritis, psoriasis, atopic dermatitis and hypothyroidism are excepted.
• A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Concomitant therapy with any other anti-cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs.
• Has a known additional malignancy that is progressing or requires active treatment.
• Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 150 days after the last dose of study drug.
• A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate in the opinion of the treating investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Sweden · 1 center

• Sahlgrenska University Hospital — Gothenburg

Identifiers

NCT: NCT07349303 · 2024-519594-19-00 · 2024-519594-19-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗