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Prostaglandin Inhibition and PD-1/CTLA4 Blockade in Melanoma

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ClinicalTrials.gov Identifier: NCT03396952
Recruitment Status : Recruiting
First Posted : January 11, 2018
Last Update Posted : March 1, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Drug: Aspirin Biological: Ipilimumab Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prostaglandin Inhibition and PD-1/CTLA4 Blockade in Melanoma
Actual Study Start Date : January 25, 2018
Estimated Primary Completion Date : June 7, 2022
Estimated Study Completion Date : June 7, 2023


Arm Intervention/treatment
Experimental: Treatment (pembrolizumab, ipilimumab, aspirin)
Patients 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.
Drug: Aspirin
Given PO
Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475




Primary Outcome Measures :
  1. 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 ]
    Point estimates of ORR and 95% confidence intervals will be provided.


Secondary Outcome Measures :
  1. 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 ]
  2. Overall survival (OS) [ Time Frame: From study day 1 to death due to any cause, assessed up to 4.5 years ]
    The median duration of OS will be estimated using the Kaplan-Meier methods with the associated confidence intervals.

  3. 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) ]
    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.



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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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/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 malignancy except localized prostate cancer, basal or squamous cell skin cancer, localized cervical cancer or breast cancer that has been curatively treated
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03396952


Locations
United States, California
University of Califonia, San Francisco Recruiting
San Francisco, California, United States, 94115
Contact: Adil I. Daud    877-827-3222    cancertrials@ucsf.edu   
Principal Investigator: Adil I. Daud         
Sponsors and Collaborators
University of California, San Francisco
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Adil Daud University of California, San Francisco

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03396952     History of Changes
Other Study ID Numbers: 17854
NCI-2017-02441 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17-23429
17854 ( Other Identifier: University of California, San Francisco )
First Posted: January 11, 2018    Key Record Dates
Last Update Posted: March 1, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Aspirin
Antibodies, Monoclonal
Antineoplastic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Immunologic Factors