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| Overall Recruitment Status: Enrollment complete |
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| Official Title |
| (S1801) A Phase II Randomized Study of Adjuvant vs. Neoadjuvant MK-3475 (Pembrolizumab) for Clinically Detectable Stage III-IV High-Risk Melanoma |
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| Region |
Sponsors |
| Colorado |
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| Acronym |
NCT No. |
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NCT03698019 |
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| Study Type |
Phase |
| Clinical Trial |
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| Purpose |
| This phase II trial studies how pembrolizumab works before and after surgery in treating patients with stage III-IV high-risk melanoma. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab before and after surgery may work better in treating melanoma. |
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| Detailed Description |
| PRIMARY OBJECTIVE:
I. To compare event-free survival (EFS) in participant with high-risk resectable melanoma randomized to neoadjuvant MK-3475 (pembrolizumab) with participants randomized to adjuvant MK-3475 (pembrolizumab).
SECONDARY OBJECTIVES:
I. To assess the frequency and severity of toxicities on each of the arms. II. To compare between arms overall survival (OS), disease control at 24 weeks, locoregional control in the surgical site(s), and total number of MK-3475 (pembrolizumab) doses received.
III. On the neoadjuvant arm, to estimate the pathologic response rate, the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 response rate (confirmed and unconfirmed complete response [CR] and partial response [PR]), and the immune-related (i)RECIST response rate (confirmed and unconfirmed CR and PR), before surgical resection; to compare definitions of pathologic partial response; and to evaluate the association between pathologic response and EFS and OS.
IV. To describe the proportion of participants on each arm who received the surgery planned at randomization.
ADDITIONAL OBJECTIVE:
I. To bank tumor tissue and whole blood in anticipation of future correlative studies in this participant population.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Within 17 days (preferably within 14 days) days after surgical resection, patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for 18 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive pembrolizumab IV over 30 minutes on day 1 every 3 weeks for 3 cycles, then undergo surgical resection within 3 weeks. Within 84 days, patients receive pembrolizumab IV over 30 minutes every 3 weeks for 15 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3 and 12 weeks, then every 3 months for 2 years, every 6 months for 3 years, then every 12 months for up to a total of 10 years. |
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- Patients may have received prior radiation therapy, including after prior surgical resection. All adverse events associated with prior surgery and radiation therapy must have resolved to =< Grade 1 prior to randomization.
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All patients must have a CT or magnetic resonance imaging (MRI) of the brain within 42 days prior to randomization. The brain CT or MRI should be performed with intravenous contrast (unless contraindicated).
Absolute neutrophil count (ANC) >= 1,500/microliter (mcL) (within 42 days prior to randomization).
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Platelets >= 100,000/mcL (within 42 days prior to randomization).
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Hemoglobin >= 10 g/dL (within 42 days prior to randomization).
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Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except patients with Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 42 days prior to randomization).
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Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2 x IULN (within 42 days prior to randomization).
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Alkaline phosphatase =< 2 x IULN (within 42 days prior to randomization).
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Patients must have lactate dehydrogenase (LDH) performed within 42 days prior to randomization.
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Patients must have adequate creatinine clearance as evidenced by creatinine clearance (CrCl) > 30 mL/min within 42 days prior to randomization.
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Patients must have Zubrod Performance Status =< 2.
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Please contact study personnel for more eligibility criteria
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- Patients must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
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Patients must not have an active infection requiring systemic therapy.
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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.
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Patients must not have received live vaccines within 42 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin (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.
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Patients must not have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to randomization. Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority.
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Please contact study personnel for more eligibility criteria
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Antineoplastic Agents, Immunological
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Neoplasms by Histologic Type
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Neoplasms, Germ Cell and Embryonal
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