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Prostaglandin Inhibition and Immune Checkpoint Blockade in Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03396952
Recruitment Status : Active, not recruiting
First Posted : January 11, 2018
Results First Posted : June 10, 2021
Last Update Posted : June 10, 2021
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 Stage IIIA Cutaneous Melanoma Stage IIIB Cutaneous Melanoma Stage IIIC Cutaneous Melanoma Stage IV Cutaneous Melanoma 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prostaglandin Inhibition and Programmed Cell Death Protein 1 (PD-1)/Cytotoxic T-lymphocyte-Associated Protein 4 (CTLA4) Blockade in Melanoma
Actual Study Start Date : April 19, 2018
Actual Primary Completion Date : April 30, 2020
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

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) [ Time Frame: Up to 12 weeks ]
    Defined as the proportion of subjects for whom the best overall response at week 12 is confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST). Point estimates of ORR and 95% confidence intervals will be provided. Only participants with confirmed response are included in this analysis.


Secondary Outcome Measures :
  1. Number of Participants With Reported Treatment-related Adverse Events [ Time Frame: Within 30 days after last dose of study drug, up to 3 years ]
    Number of participants with reported treatment-related adverse events defined as having an attribution of definite, possible, and probable according to Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be reported.

  2. Proportion of Participants With Progression-free Survival (PFS) at 6 Months [ Time Frame: Up to 6 months (182 days) ]
    PFS at 6 months is defined as the proportion of subjects alive and progression-free 6 months (182 days) after study day 1.

  3. Duration of PFS [ Time Frame: Assessed up to 4.5 years ]
    Defined as the time from the study day 1 to the earlier of disease progression or death due to any cause

  4. Overall Survival (OS) [ Time Frame: Assessed up to 4.5 years ]
    Duration of OS is defined as the time from study day 1 to death due to any cause. For subjects who are alive at the time of data cutoff or are permanently lost to follow-up, duration of OS will be right censored at the date the subject was last known to be alive.The median duration of OS will be estimated using the Kaplan-Meier methods with the associated confidence intervals



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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/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

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
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United States, California
University of Califonia, San Francisco
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Adil Daud, MD University of California, San Francisco
  Study Documents (Full-Text)

Documents provided by University of California, San Francisco:
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03396952    
Other Study ID Numbers: 17854
NCI-2017-02441 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: January 11, 2018    Key Record Dates
Results First Posted: June 10, 2021
Last Update Posted: June 10, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Melanoma
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Skin Diseases
Aspirin
Pembrolizumab
Ipilimumab
Antineoplastic Agents, Immunological
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