Clinical Trials /

Prostaglandin Inhibition and Immune Checkpoint Blockade in Melanoma

NCT03396952

Description:

This phase II trial studies how well pembrolizumab, ipilimumab, and aspirin work in treating patients with melanoma that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Aspirin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab, ipilimumab, and aspirin may work better in treating patients with melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Prostaglandin Inhibition and Immune Checkpoint Blockade in Melanoma
  • Official Title: Prostaglandin Inhibition and Programmed Cell Death Protein 1 (PD-1)/Cytotoxic T-lymphocyte-Associated Protein 4 (CTLA4) Blockade in Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 17854
  • SECONDARY ID: NCI-2017-02441
  • SECONDARY ID: 17854
  • NCT ID: NCT03396952

Conditions

  • Stage III Cutaneous Melanoma
  • Stage IIIA Cutaneous Melanoma
  • Stage IIIB Cutaneous Melanoma
  • Stage IIIC Cutaneous Melanoma
  • Stage IV Cutaneous Melanoma

Interventions

DrugSynonymsArms
AspirinAcetylsalicylic Acid (ASA), Aspergum, Ecotrin, Empirin, Entericin, Extren, MeasurinTreatment (pembrolizumab, ipilimumab, aspirin)
IpilimumabAnti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyTreatment (pembrolizumab, ipilimumab, aspirin)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, ipilimumab, aspirin)

Purpose

This phase II trial studies how well pembrolizumab, ipilimumab, and aspirin work in treating patients with melanoma that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Aspirin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab, ipilimumab, and aspirin may work better in treating patients with melanoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the overall response rate (ORR) by week 12 in patients with stage III
      unresectable/stage IV melanoma.

      SECONDARY OBJECTIVES:

      I. To determine the median progression free survival, overall survival, and toxicity profile
      of the combination of ipilimumab, pembrolizumab and high dose aspirin in patients with stage
      III unresectable/IV melanoma.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1, ipilimumab IV
      over 60 minutes on day 1 for courses 1-4, and aspirin orally (PO) twice daily (BID) on days
      1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up for 30 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab, ipilimumab, aspirin)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1, ipilimumab IV over 60 minutes on day 1 for courses 1-4, and aspirin PO BID (orally, twice a day) on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Aspirin
  • Ipilimumab
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically confirmed melanoma that is metastatic or
             unresectable and for which standard curative or palliative measures do not exist or
             are no longer effective

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          -  Leukocytes >= 3,000/microliter (mcL)

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  Total bilirubin =< 1.5 X institutional upper limit

          -  Aspartate aminotransferase (AST) [serum glutamic-oxaloacetic transaminase (SGOT)] =<
             2.5 X institutional upper limit of normal

          -  Alanine aminotransferase (ALT) [serum glutamate pyruvate transaminase (SGPT)] =< 2.5 X
             institutional upper limit of normal

          -  Creatinine =< 1.5 X upper limit of normal (ULN)

          -  Women of childbearing potential should have a negative urine or serum pregnancy within
             72 hours prior to receiving the first dose of study drug; if the urine test is
             positive or cannot be confirmed as negative, a serum pregnancy test will be required

          -  Women of childbearing potential must be willing to use an adequate method of
             contraception, for the course of the study through 120 days after the last dose of
             study medication; Note: Abstinence is acceptable if this is the usual lifestyle and
             preferred contraception for the subject

          -  Men of childbearing potential must agree to use an adequate method of contraception,
             starting with the first dose of study therapy through 120 days after the last dose of
             study therapy; Note: Abstinence is acceptable if this is the usual lifestyle and
             preferred contraception for the subject

          -  Ability to understand a written informed consent document, and the willingness to sign
             it

        Exclusion Criteria:

          -  Any mental or physical condition or disease or past medical history that mitigates
             against following the protocol

          -  History of active autoimmune diseases such as but not limited to Crohn?s disease,
             ulcerative colitis, Sjogren's syndrome, requiring active immune suppression; patient
             may have hay fever or controlled asthma

          -  Any solid organ transplant or bone marrow transplant

          -  Any other disseminated malignancy. Exceptions include: localized prostate cancer,
             basal or squamous cell skin cancer, localized cervical cancer, and localized breast
             cancer.

          -  Uncontrolled central nervous system (CNS) metastasis; patients with CNS metastasis can
             be eligible if definitively treated with radiotherapy or surgery

          -  Any coexistent medical condition interfering with drug absorption

          -  History of gastritis or malabsorption syndrome or aspirin intolerance or allergy

          -  Live vaccination within the last 30 days

          -  History of multiple sclerosis, type 1 diabetes mellitus (DM) or Guillain-Barre
             syndrome

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 120 days
             after the last dose of trial treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) defined as the proportion of subjects for whom the best overall response at the time of data cutoff is confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame:Up to 12 weeks
Safety Issue:
Description:Point estimates of ORR and 95% confidence intervals will be provided.

Secondary Outcome Measures

Measure:Incidence of adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4
Time Frame:Up to 30 days after last dose
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:From study day 1 to death due to any cause, assessed up to 4.5 years
Safety Issue:
Description:The median duration of OS will be estimated using the Kaplan-Meier methods with the associated confidence intervals.
Measure:Profession free survival (PFS) according to RECIST
Time Frame:From the study day 1 to the earlier of disease progression or death due to any cause, assessed up to 6 months (182 days)
Safety Issue:
Description:95% confidence intervals will be provided. Median of PFS and duration of PFS will also be estimated using Kaplan-Meier methods with associated confidence intervals.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, San Francisco

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