Prostaglandin Inhibition and Immune Checkpoint Blockade in Melanoma

NCT03396952 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17854NCI-2017-02441
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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.

  Up to 12 weeks

Secondary Outcomes (4)

• Number of Participants With Reported Treatment-related Adverse Events

  Within 30 days after last dose of study drug, up to 3 years

• Proportion of Participants With Progression-free Survival (PFS) at 6 Months

  Up to 6 months (182 days)

• Median Duration of PFS

  Up to 3 years

• Median Overall Survival (OS)

  Up to 3 years

Study Arms (1)

Treatment (pembrolizumab, ipilimumab, aspirin)

EXPERIMENTAL

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; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Aspirin DRUG

Given PO

Also known as: Acetylsalicylic Acid (ASA), Aspergum, Ecotrin, Empirin, Entericin, Extren, Measurin

Treatment (pembrolizumab, ipilimumab, aspirin)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Treatment (pembrolizumab, ipilimumab, aspirin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, ipilimumab, aspirin)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, ipilimumab, aspirin)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Califonia, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Aspirin; Ipilimumab; CTLA-4 Antigen; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Results Point of Contact

• Title: Dr. Adil Daud, MD
• Organization: University of California, San Francisco

Adil.Daud@ucsf.edu

(415) 353-7392

Study Officials

• Adil Daud, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: January 11, 2018
• Study Start: April 19, 2018
• Primary Completion: April 30, 2020
• Study Completion: June 30, 2022
• Last Updated: October 13, 2022
• Results First Posted: June 10, 2021

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)