Stage IIB/IIC and microscopic stage III BRAF V600-mutant melanoma
Conditions
Interventions
Arm A: Adjuvant systemic therapy with pembrolizumab (200 mg every 3 weeks or 400 mg every 6 weeks), or nivolumab (240 mg every 2 weeks or 480 mg every 4 weeks) for 1 year
Arm B: Adjuvant systemic ther
Sponsors
Namikawa Kenjiro
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Histologically proven melanoma (2) Meeting either (i) or (ii) according to the AJCC TNM classification, 8th edition. (i) All of the following are fullfilled. - Pathological diagnosis from surgical specimen showing T3b-T4b. - No evidence of clinically detectable (macroscopic ) lymph node metastasis. (ii) All of the following are fullfilled. - Pathological diagnosis from surgical specimen showing T0-T3a. - Presence of at least one of the following: microscopic lymph node metastasis, satellite metastasis, or in-transit metastasis. - No evidence of clinically detectable (macroscopic) lymph node metastasis. (3) No evidence of distant metastasis based on the physical examination and contrast-enhanced CT scan (head to groin). (4) Presence of BRAF V600 mutation confirmed using an in vitro diagnostic assay approved in Japan. (5) Complete pathological resection of all known lesions (primary tumor, satellite metastases, and in-transit metastases). (6) Postoperative period for melanoma is 7-63 days (7) Age >=18 years. (8) ECOG performance status, 0 or 1. (9) Ability to swallow and retain oral medication (10) No previous treatment with immune checkpoint inhibitors, BRAF inhibitors, or MEK inhibitors. (11) No autoimmune disease, except well-controlled type 1 diabetes, hyperthyroidism or hypothyroidism requiring only oral therapy, and autoimmune skin diseases requiring no systemic therapy (such as pemphigus, psoriasis vulgaris, pemphigoid, or vitiligo vulgaris) (12) Adequate organ function (assessed within 28 days prior to registration): (i) Neutrophil count >=1,200/mm3 (ii) Hemoglobin >=8.0 g/dL, without blood transfusion within 14 days of blood test (iii) Platelet count >=100,000/mm3 (iv) Total bilirubin <=2.0 mg/dL (v) Aspartate transaminase <=100 U/L (vi) Alanine transaminase <=100 U/L (vii) Serum creatinine <=1.5 mg/dL (13) Written informed consent.
Exclusion criteria
Exclusion criteria: (1) Synchronous or metachronous (within 5 years) malignancies. (2) Infectious disease requiring systemic treatment. (3) Pyrexia of 38 degrees centigrade or higher. (4) Female during pregnancy, within 28 days of postparturition, or during lactation, and male expecting partner's pregnancy. (5) Severe psychological disorders. (6) Receiving continuous administration of corticosteroids at a dose of over 10 mg/day of prednisolone equivalent or immunosuppressants. (7) History of unstable angina pectoris with new onset or exacerbation within the recent 3 weeks or myocardial infarction within 6 months before registration. (8) Poorly controlled valvular disease, dilated cardiomyopathy, or hypertrophic cardiomyopathy. (9) New York Heart Association (NYHA) class II to IV heart failure (10) Clinically serious arrhythmia on the electrocardiogram. (11) Interstitial pneumonia, pulmonary fibrosis, or severe emphysema on chest CT. (12) Gastrointestinal disorders that may interfere with drug absorption, such as malabsorption syndromes or extensive resection of the gastrointestinal tract. (13) Current or prior history of retinal vein occlusion or central serous retinopathy. (14) History of organ transplantation, including hematopoietic stem cell transplantation. (15) Positive for HIV antibody.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relapse-free survival | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of persistent adverse events (proportion of patients with persistent grade >=2 treatment-related adverse events at the earliest of 3 years after initiation of adjuvant therapy, death, or initiation of subsequent systemic therapy), overall survival, distant metastasis-free survival, pattern of recurrence, incidence of adverse events, proportion of quality of life preservation | — |
Contacts
Public ContactKenjiro Namikawa
National Cancer Center Hospital
Outcome results
None listed