Clinical Trials /

Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by Surgery

NCT02775851

Description:

This pilot phase II trial studies how well pembrolizumab works in treating patients with desmoplastic melanoma (DM) that can or cannot be removed by surgery (unresectable). 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.

Related Conditions:
  • Desmoplastic Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by Surgery
  • Official Title: A Phase II and Pilot Trial of PD-1 Blockade With MK-3475 (Pembrolizumab) in Patients With Resectable or Unresectable Desmoplastic Melanoma (DM)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2016-00666
  • SECONDARY ID: NCI-2016-00666
  • SECONDARY ID: S1512
  • SECONDARY ID: S1512
  • SECONDARY ID: S1512
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT02775851

Conditions

  • Desmoplastic Melanoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Cohort A (pembrolizumab, surgery)

Purpose

This pilot phase II trial studies how well pembrolizumab works in treating patients with desmoplastic melanoma (DM) that can or cannot be removed by surgery. Monoclonal antibodies, like pembrolizumab, may block specific proteins which may strengthen the immune system and control tumor growth.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the pathologic complete response rate (pCR) in patients with resectable
      desmoplastic melanoma treated with neoadjuvant MK-3475 (pembrolizumab). (Cohort A) II. To
      evaluate the complete response rate (confirmed and unconfirmed) in patients with unresectable
      desmoplastic melanoma treated with MK-3475 (pembrolizumab). (Cohort B)

      SECONDARY OBJECTIVES:

      I. To estimate the 9 week response rate (RR) (unconfirmed complete and partial responses)
      among patients with measurable disease. (Cohort A) II. To estimate the median overall
      survival (OS). (Cohort A) III. To evaluate safety and tolerability of MK-3475 (pembrolizumab)
      in the neoadjuvant setting. (Cohort A) IV. To estimate the median progression-free survival
      (PFS). (Cohort B) V. To estimate the median overall survival (OS). (Cohort B) VI. To evaluate
      safety and tolerability of MK-3475 (pembrolizumab) in this setting. (Cohort B)

      TERTIARY OBJECTIVES:

      I. To evaluate the hypothesis that higher mutational load in the patient derived baseline
      tumor biopsy samples is associated with higher pathologic complete response (pCR).

      II. To evaluate T cell infiltration into the tumors in DM patients and correlate with
      response to programmed cell death protein 1 (PD-1) blockade.

      III. To evaluate the clonality of tumor infiltrating T cells in DM patients and correlate
      with response to PD-1 blockade.

      IV. To evaluate adaptive immune resistant mechanism in DM tumors.

      OUTLINE: Patients are assigned to 1 of 2 cohorts.

      COHORT A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1.
      Treatment repeats every 21 days for up to 3 courses. Patients with potentially resectable
      disease undergo surgery. Patients with tumor progression and unresectable disease may receive
      one additional course of pembrolizumab.

      COHORT B: Patients with unresectable disease receive pembrolizumab IV over 30 minutes on day
      1. Treatment repeats every 21 days for up to 34 courses in the absence of disease progression
      or toxicity.

      After completion of study treatment, patients are followed up at 6 and 12 weeks, then every 3
      months for 1 year, and every 6 months for 4 years.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort A (pembrolizumab, surgery)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 courses. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional course of pembrolizumab.
  • Pembrolizumab
Cohort B (pembrolizumab)Active ComparatorPatients with unresectable disease receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 courses in the absence of disease progression or toxicity.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  COHORT A: Patients 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; patients 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 OR

          -  COHORT B: Patients must have histologically or cytologically confirmed primary
             desmoplastic melanoma that is unresectable; patients 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 a contrast
             enhanced CT of the chest, abdomen and pelvis; imaging of the head and neck is required
             only if the 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, photograph with a
             ruler included and physician measurements, must be kept in the patient's chart as
             source documentation; 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; all disease must be assessed and documented on the baseline
             tumor assessment form (RECIST 1.1)

          -  Patients must not have 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

          -  Patients must not have received prior systemic treatment for this melanoma

          -  Patients must not be planning to receive concomitant other biologic therapy, radiation
             therapy, hormonal therapy, other chemotherapy, anti-cancer surgery or other
             anti-cancer therapy while on this protocol

          -  Patients must not have received radiation therapy, non-cytotoxic agents or
             investigational agents or systemic corticosteroids within 14 days prior to
             registration

          -  Patients may have received prior surgery; all adverse events associated with prior
             surgery must have resolved to =< grade 1 (per Common Terminology Criteria for Adverse
             Events [CTCAE] 4.0) prior to registration

          -  Obtained within 28 days prior to registration: Absolute neutrophil count (ANC) >=
             1,500/mcl

          -  Obtained within 28 days prior to registration: Platelets >= 50,000/mcl

          -  Obtained within 28 days prior to registration: Hemoglobin >= 8 g/dL

          -  Obtained within 28 days prior to registration: Total bilirubin =< 1.5 x institutional
             upper limit of normal (IULN) (or =< 3.0 x IULN with Gilbert's syndrome)

          -  Obtained within 28 days prior to registration: Aspartate aminotransferase (AST) and
             alanine aminotransferase (ALT) =< 2.5 x IULN (or < 5 x IULN for patients with known
             liver metastases)

          -  Patients must have lactate dehydrogenase (LDH) performed within 28 days prior to
             registration

          -  Patients must have Zubrod performance status =< 2

          -  Patients must not have 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, 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 < 25,000 IU/ml; patients must be
             on a stable anti-viral therapy

          -  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

          -  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 have
             agreed to use an effective contraceptive method for the course of the study through
             120 days after the last dose of study medication; should a woman become pregnant or
             suspect she is pregnant while she or her partner is participating in this study, she
             should inform her treating physician immediately; a woman is considered to be of
             "reproductive potential" if she has had menses at any time in the preceding 12
             consecutive months; in addition to routine contraceptive methods, "effective
             contraception" also includes heterosexual celibacy and surgery intended to prevent
             pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
             bilateral oophorectomy, or bilateral tubal ligation; however, if at any point a
             previously celibate patient chooses to become heterosexually active during the time
             period for use of contraceptive measures outlined in the protocol, he/she is
             responsible for beginning contraceptive measures; patients must not be pregnant or
             nursing

          -  Patients must have specimens available and institutions must be planning to submit for
             centralized pathology review and for integrated translational medicine objectives

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines

          -  As a part of the Oncology Patient Enrollment Network (OPEN) registration process, the
             treating institution's identity is provided in order to ensure that the current
             (within 365 days) date of institutional review board approval for this study has been
             entered in the system
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic complete response (pCR) rate (Cohort A)
Time Frame:Up to 5 years
Safety Issue:
Description:Pathologic complete response is defined as no evidence of viable tumor cells on complete pathological evaluation of the surgical specimen per institutional standard of care. Will assess the association between overall mutational load and pCR rate.

Secondary Outcome Measures

Measure:Overall response rate (Cohort A)
Time Frame:At 9 weeks
Safety Issue:
Description:Estimated with a 95% confidence interval.
Measure:Overall survival rate (Cohort A and B)
Time Frame:At 9 weeks
Safety Issue:
Description:Estimated with a 95% confidence interval.
Measure:Progression free survival (Cohort A and B)
Time Frame:At 9 weeks
Safety Issue:
Description:Estimated with a 95% confidence interval.
Measure:Incidence of toxicity as measured by the National Cancer Institute Common Terminology for Adverse Events version 4.0 (Cohort A)
Time Frame:Up to 9 weeks
Safety Issue:
Description:Toxicity will be assessed across all patients receiving pembrolizumab.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

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