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Prostaglandin Inhibition and Immune Checkpoint Blockade in Melanoma

Primary Purpose

Stage III Cutaneous Melanoma, Stage IIIA Cutaneous Melanoma, Stage IIIB Cutaneous Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aspirin
Ipilimumab
Laboratory Biomarker Analysis
Pembrolizumab
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage III Cutaneous Melanoma

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Califonia, San Francisco

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (pembrolizumab, ipilimumab, aspirin)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of Participants With Reported Treatment-related Adverse Events
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.
Proportion of Participants With Progression-free Survival (PFS) at 6 Months
PFS at 6 months is defined as the proportion of subjects alive and progression-free 6 months (182 days) after study day 1.
Median Duration of PFS
Duration of PFS is defined as the time from the study day 1 to the earlier of disease progression or death due to any cause. The analysis of PFS will include only objective progression events per RECIST and clinical progression determined by the investigator may not be considered disease progression. The median duration of PFS will be estimated using the Kaplan-Meier methods with the associated 95% confidence interval.
Median Overall Survival (OS)
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 95% confidence interval.

Full Information

First Posted
January 5, 2018
Last Updated
September 19, 2022
Sponsor
University of California, San Francisco
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03396952
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
April 19, 2018 (Actual)
Primary Completion Date
April 30, 2020 (Actual)
Study Completion Date
June 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III Cutaneous Melanoma, Stage IIIA Cutaneous Melanoma, Stage IIIB Cutaneous Melanoma, Stage IIIC Cutaneous Melanoma, Stage IV Cutaneous Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (pembrolizumab, ipilimumab, aspirin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Aspirin
Other Intervention Name(s)
Acetylsalicylic Acid (ASA), Aspergum, Ecotrin, Empirin, Entericin, Extren, Measurin
Intervention Description
Given PO
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, Lambrolizumab, MK-3475, SCH 900475
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
Up to 12 weeks
Secondary Outcome Measure Information:
Title
Number of Participants With Reported Treatment-related Adverse Events
Description
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.
Time Frame
Within 30 days after last dose of study drug, up to 3 years
Title
Proportion of Participants With Progression-free Survival (PFS) at 6 Months
Description
PFS at 6 months is defined as the proportion of subjects alive and progression-free 6 months (182 days) after study day 1.
Time Frame
Up to 6 months (182 days)
Title
Median Duration of PFS
Description
Duration of PFS is defined as the time from the study day 1 to the earlier of disease progression or death due to any cause. The analysis of PFS will include only objective progression events per RECIST and clinical progression determined by the investigator may not be considered disease progression. The median duration of PFS will be estimated using the Kaplan-Meier methods with the associated 95% confidence interval.
Time Frame
Up to 3 years
Title
Median Overall Survival (OS)
Description
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 95% confidence interval.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adil Daud, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Califonia, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Prostaglandin Inhibition and Immune Checkpoint Blockade in Melanoma

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