High risk resected melanoma.
Conditions
Interventions
Trade Name: KEYTRUDA®
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
Other descriptive name: Pembrolizumab
Concentrati
Sponsors
Irish Clinical Oncology Research Group CLG, trading as Cancer Trials Ireland
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Principal inclusion criteria are listed below. Please refer to the study protocol for full criteria. STEP 1 REGISTRATION Disease Related Criteria • Patients must have completely resected melanoma of cutaneous origin or of unknown primary. Patients must be classified as Stage IIIA (N2a), IIIB, IIIC, or Stage IV melanoma. Patients with non-ulcerated T1b N1a disease are not eligible. Patients with melanoma of mucosal or other non-cutaneous origin are eligible. Patients with melanoma of ocular origin are not eligible. Patients with a history of brain metastases are ineligible. • Patients are eligible for this trial either at initial presentation of their melanoma or at the time of the first detected nodal, satellite/in-transit, distant metastases, or recurrent disease in prior lymphadenectomy basin or distant site. Nodal, satellite/in-transit metastasis, distant metastases or disease in a prior complete lymphadenectomy basin must have been confirmed histologically by H & E stained slides. • Patients with multiple regional nodal basin involvement are eligible. Gross or microscopic extracapsular nodal extension is permitted. • Patients at initial presentation of melanoma must undergo an adequate wide excision of the primary lesion, if present. Patients with previously diagnosed melanoma must have had all current disease resected with pathologically negative margins & must have no evidence of disease at the primary site or must undergo re-resection of the primary site. A full lymphadenectomy is required for all node-positive patients including those with positive sentinel nodes. Patients with recurrent disease who have had a prior complete lymphadenectomy fulfill this requirement as long as all recurrent disease has been resected. For all patients, all disease must have been resected with negative pathological margins & no clinical, radiologic, or pathological evidence of any incompletely resected melanoma. Patients must be registered within 98 days of the last surgery performed to render the patient free of disease. Specimen Submission Criteria • Patients must have available&be willing to submit a minimum of 5 unstained slides from primary, lymph node, or metastatic site to determine PD-L1 expression. • Patients must be offered the opportunity to participate in specimen banking. • Patients must be willing to have blood draws for PK/ADA analysis (MK-3475 arm). Prior/Concurrent Therapy Criteria • Patients may have received prior radiation therapy, including after the surgical resection. All AEs associated with prior surgery & radiation therapy must have resolved to = Grade 1 prior to registration. Clinical/Laboratory Criteria • Patients must be = 18 years of age. • All patients must have disease-free status documented by a complete physical exam & imaging studies within 42 days prior to registration. Refer to protocol for imaging requirements. • All patients must have a CT or MRI of the brain within 90 days prior to registration (with intravenous contrast (unless contraindicated)). • Adequate bone marrow function as evidenced by all of the following: ANC = 1,500 mcL; platelets = 100,000/mcL; Hemoglobin = 10 g/dL. • Adequate hepatic function as evidenced by the following: total bilirubin = 1.5 x institutional upper limit of normal (IULN) (except Gilbert’s Syndrome, who must have a total bilirubin < 3.0 mg/dL), and SGOT (AST) and SGPT (ALT) and alkaline phosphatase = 2 x IULN. • Adequate renal function as eviden
Exclusion criteria
Exclusion criteria: Principal exclusion criteria are listed below. Please refer to the study protocol for full criteria. STEP 1 REGISTRATION Prior/Concurrent Therapy Criteria • Patients must not have received neoadjuvant treatment for their melanoma. Patients must not have had prior immunotherapy including, but not limited to ipilimumab, interferon alfa-2b, high dose IL-2, PEG-IFN, anti-PD-1, anti-PD-L1 intra-tumoral or vaccine therapies. Patients must not be planning to receive any of the prohibited therapies listed in protocol Section 7.2 during the screening or treatment phases of the study. • Patients must not be planning to receive concomitant other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, surgery or other therapy after Step 2 registration. Clinical/Laboratory Criteria • Patients must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. • Patients must not have an active infection requiring systemic therapy. • Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 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. • Patients must not have received live vaccines within 42 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. • Patients must not have known active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection prior to registration. • Patients must not have a history or current evidence of any condition, therapy or laboratory abnormality that might confound the trial results, interfere with the patient's participation for the full duration of the trial, or indicate that participation in the trial is not in the patient's best interests, in the opinion of the treating investigator. Clinical Laboratory • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinoma of the breast in situ, atypical melanocytic hyperplasia or melanoma in situ, adequately treated Stage I or II cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: a. To compare overall survival (OS) of patients with resected Stage III and IV melanoma treated with physician/patient choice of either high dose interferon alfa-2b or ipilimumab versus MK-3475 (pembrolizumab) b. Among patients who are PD-L1 positive, to compare OS of patients with resected Stage III and IV melanoma treated with physician/patient choice of either high dose interferon alfa-2b or ipilimumab versus MK-3475 (pembrolizumab). c. To compare relapse-free survival (RFS) of patients with resected Stage III and IV melanoma treated with physician/patient choice of either high dose interferon alfa-2b or ipilimumab to MK-3475 (pembrolizumab). ;Secondary Objective: Secondary Objectives: a. Estimate OS & RFS for PD-L1 negative or PD-L1 indeterminate patients. b. Compare OS & RFS of patients between the two arms within PD-L1 positive & negative subgroups & interaction between PD-L1 (positive versus negative) & treatment arm. c. Assess safety & tolerability of the regimens. Additional Objectives: a. Bank tissue & whole blood in anticipation of future correlative studies. b. Evaluate PD-L1 expression through IHC assay. c. Evaluate effect of treatment-related side effects that may have an impact on the health-related domains of quality of life. d. Pharmacokinetic and anti-drug antibody (ADA) testing will be performed on all patients receiving MK-3475. Translational Objectives: a. Evaluate the association between TCRß variable gene (TRBV) haplotype & Grade 3-4 immune-related adverse events among Stage III melanoma patients treated w/adjuvant Ipilimumab or Pembrolizumab. b. Describe TRBV haplotype distribution. ;Primary end point(s): - Progression/Relapse - Relapse-Free Survival - Overall Survival - Performance Status;Timepoint(s) of evaluation of this end point: -Progression/Relapse: Appearance of any new lesion/site. Death due to disease without prior documentation of progression. - Relapse-Free Survival: Measured from date of randomiz | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable. ;Timepoint(s) of evaluation of this end point: Not applicable. | — |
Countries
Ireland
Contacts
Public ContactClinical Trials Information
Cancer Trials Ireland
Outcome results
None listed