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Clinical Trial 18992

Cancer Type: Cutaneous
Interventions:Pembrolizumab (Keytruda)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Zeynep Eroglu

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase II and Pilot Trial of PD-1 Blockade with MK-3475 (Pembrolizumab) in Patients with Resectable or Unsectable Desmoplastic Melanoma (DM)

Summary

The purpose of this study is to test any good and bad effects of the study drug MK-3475 (also called pembrolizumab).

Objective

1.1 Primary Objective: a.) Cohort A - To evaluate the pathologic complete response rate (pCR as defined in Section 10.0) in patients with resectable desmoplastic melanoma treated with neoadjuvant MK-3475 (pembrolizumab). b.) Cohort B - To evaluate the complete response rate (confirmed and unconfirmed) in patients with unresectable desmoplastic melanoma treated with MK-3475 (pembrolizumab). 1.2 Secondary Objectives: Cohort A a.) To estimate the 9 week response rate (RR) (unconfirmed complete and partial responses). b.) To estimate the median overall survival (OS). c.) To evaluate safety and tolerability of MK-3475 (pembrolizumab) in the neoadjuvant setting. Cohort B d.) To estimate the median progression-free survival (PFS). e.) To estimate the median overall survival (OS). f.) To evaluate safety and tolerability of MK-3475 (pembrolizumab) in this setting. 1.3 Other Objectives (all patients): a.) To evaluate the hypothesis that higher mutational load in the patient derived baseline tumor biopsy samples is associated with higher response rate (RR). b.) To evaluate T cell infiltration into the tumors in DM patients and correlate with response to PD-1 blockade. c.) To evaluate the clonality of tumor infiltrating T cells in DM patients and correlate with response to PD-1 blockade. d.) To evaluate adaptive immune resistant mechanism in DM tumors.

Inclusion Criteria

  • COHORT A: Participants must have histologically or cytologically confirmed primary desmoplastic melanoma that is deemed resectable; the decision to perform surgery on patients must be based on good clinical judgment; eligible patients for surgical resection must have disease that, in the judgment of the surgeon, is deemed completely resectable resulting in free surgical margins; must have residual disease after initial biopsy which can be measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; residual disease can either be confirmed with fine-needle aspiration (FNA) or if measurable disease is present, no FNA needs to be obtained.
  • COHORT B: Must have histologically or cytologically confirmed primary desmoplastic melanoma that is unresectable; partiacipants in Cohort B must have measurable disease per RECIST 1.1.
  • Contrast-enhanced computed tomography (CT) scans of the chest, abdomen and pelvis are required; a whole body positron emission tomography (PET)/CT scan with diagnostic quality images and intravenous iodinated contrast may be used in lieu of contrast enhanced CT of the chest, abdomen and pelvis; imaging of the head and neck is required only if patient has a head/neck primary; contrast may be omitted if the treating investigator believes that exposure to contrast poses an excessive risk to the patient; if skin lesions are being followed as measurable disease; all measurable lesions must be assessed within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration.
  • Have not received radiation therapy, non-cytotoxic agents or investigational agents or systemic corticosteroids within 14 days prior to registration
  • If have received prior surgery; all adverse events associated with surgery must have resolved to ≤ grade 1.
  • Obtained within 28 days prior to registration: Absolute neutrophil count (ANC) >= 1500/mcl; Platelets >= 100,000/mcl; Hemoglobin >= 9 g/dL; Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (or ≤ 3.0 x IULN with Gilbert's syndrome); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x IULN (or less than 5 x IULN for patients with known liver metastases)
  • Have lactate dehydrogenase (LDH) performed within 28 days prior to registration
  • Zubrod performance status ≤ 2
  • Have not 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, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are not allowed.
  • Patients known to be human immunodeficiency virus (HIV) positive are eligible if they meet the following criteria within 30 days prior to registration: stable and adequate CD4 counts (>= 350 mm^3), and serum HIV viral load of less than 25,000 IU/ml; must be on a stable anti-viral therapy.
  • Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to registration; women/men of reproductive potential must agree to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication.
  • Have specimens available and institution planning to submit for centralized pathology review and for integrated translational medicine objectives.

  • Exclusion Criteria

  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • An active infection requiring systemic therapy.
  • 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.
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated in situ cancer, 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.
  • Pregnant or nursing.
  • Known brain metastases unless brain metastases have been treated and patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 14 days prior to registration.
  • Have received prior systemic treatment for this melanoma
  • Planning to receive concomitant other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, anti-cancer surgery or other anti-cancer therapy while on this study
  • Have received radiation therapy, non-cytotoxic agents or investigational agents or systemic corticosteroids within 14 days prior to registration
  • Planning to receive concomitant other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, anti-cancer surgery or other anti-cancer therapy while on this study