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Pembrolizumab in Treating Patients With Advanced Uveal Melanoma

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ClinicalTrials.gov Identifier: NCT02359851
Recruitment Status : Terminated (Slow accrual)
First Posted : February 10, 2015
Results First Posted : April 24, 2018
Last Update Posted : September 18, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Douglas Johnson, Vanderbilt-Ingram Cancer Center

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Stage IIIA Uveal Melanoma
Stage IIIB Uveal Melanoma
Stage IIIC Uveal Melanoma
Stage IV Uveal Melanoma
Interventions Biological: Pembrolizumab
Other: Laboratory Biomarker Analysis
Enrollment 5
Recruitment Details The recruitment period for this trial was May 2015 to January 2017. The trial was conducted at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee and University of Chicago in Chicago, Illinois This trial closed due to slow accrual.
Pre-assignment Details  
Arm/Group Title Treatment (Pembrolizumab)
Hide Arm/Group Description

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Pembrolizumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Period Title: Overall Study
Started 5
Completed 3
Not Completed 2
Reason Not Completed
Death             1
Disease progression             1
Arm/Group Title Treatment (Pembrolizumab)
Hide Arm/Group Description

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Pembrolizumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Baseline Participants 5
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
<=18 years
0
   0.0%
Between 18 and 65 years
3
  60.0%
>=65 years
2
  40.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants
61  (16.7332)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Female
1
  20.0%
Male
4
  80.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
5
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 5 participants
5
1.Primary Outcome
Title Objective Response Rate (ORR), Defined as the Percentage of Patients Achieving a Confirmed Complete or Partial Response, as Defined by Immune-related Response Criteria (irRC)
Hide Description Of note, response rates by RECIST 1.1 criteria will also be assessed although irRC will be used for the primary endpoint. The percentage of complete or partial response is calculated and 95% confidence interval is estimated using Wilson method.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patients received pembrolizumab treatment and evaluated for response.
Arm/Group Title Treatment (Pembrolizumab)
Hide Arm/Group Description:

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Pembrolizumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 4
Mean (95% Confidence Interval)
Unit of Measure: % of patients achieving response
25
(1.3 to 69.9)
2.Secondary Outcome
Title Progression-Free Survival (PFS) Defined as Time From Treatment to Progression Defined by RECIST1.1 Criteria or Death.
Hide Description PFS will be summarized using the method of Kaplan and Meier. Median PFS time with 95% confidence intervals will be reported. Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), progression will be defined as ≥ 20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest diameter recorded or the appearance of one or more new lesions, and/or appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions.
Time Frame Time from the first dose of pembrolizumab to progression, assessed up to 3 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients received treatment.
Arm/Group Title Treatment (Pembrolizumab)
Hide Arm/Group Description:

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Pembrolizumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 5
Median (95% Confidence Interval)
Unit of Measure: months
36.0 [1] 
(NA to NA)
[1]
Insufficient patient data.
3.Secondary Outcome
Title Overall Survival (OS) Defined as Number of Patients Surviving up to 3 Years.
Hide Description The Kaplan-Meier method will be used to estimate the overall survival. Median survival and its 95% confidence interval will be estimated and reported.
Time Frame Interval between the first dose of pembrolizumab and death for any reason, assessed up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patients received pembrolizumab treatment.
Arm/Group Title Treatment (Pembrolizumab)
Hide Arm/Group Description:

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Pembrolizumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 5
Measure Type: Count of Participants
Unit of Measure: Participants
Survived
3
  60.0%
Died
2
  40.0%
4.Secondary Outcome
Title Response Duration
Hide Description If sample size permits, response duration will be summarized descriptively using Kaplan-Meier medians and quartiles. Only the subset of patients who show a complete response or partial response will be included in this analysis.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Only 1 participant had a RECIST-defined response, which is ongoing and lasting 23.5 months.
Arm/Group Title Treatment (Pembrolizumab)
Hide Arm/Group Description:

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Pembrolizumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: months
23.5
5.Secondary Outcome
Title Number of Patients With Each Worst-Grade Toxicity. Incidence of Adverse Events, Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Hide Description Count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening; grade 5, death. This endpoint will be reported descriptively without formal statistical analysis.
Time Frame Up to 30 days after the last dose of trial treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Pembrolizumab)
Hide Arm/Group Description:

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Pembrolizumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 4
Measure Type: Count of Participants
Unit of Measure: Participants
Number of participants with worst-grade toxicity 1
1
  25.0%
Number of participants with worst-grade toxicity 2
1
  25.0%
Number of participants with worst-grade toxicity 3
0
   0.0%
Number of participants with worst-grade toxicity 4
1
  25.0%
Number of participants with worst-grade toxicity 5
1
  25.0%
6.Other Pre-specified Outcome
Title Changes in GNAQ/GNA11 Mutation Status on Each Patient Per Institutional Protocol
Hide Description Differences in PFS and OS between subgroups will be assessed by the stratified logrank test. Differences in ORR between subgroups will be assessed by the Pearson chi-square test. No adjustments will be made for multiple comparisons.
Time Frame Baseline up to 2 years
Outcome Measure Data Not Reported
7.Other Pre-specified Outcome
Title Change in PD-L1 Expression Status on Archival or Fresh Tissue From All Patients and Correlate With ORR
Hide Description Differences in PFS and OS between subgroups will be assessed by the stratified logrank test. Differences in ORR between subgroups will be assessed by the Pearson chi-square test. No adjustments will be made for multiple comparisons.
Time Frame Baseline up to 2 years
Outcome Measure Data Not Reported
8.Other Pre-specified Outcome
Title Changes in Molecular Characteristics of Uveal Melanoma When Treated With Pembrolizumab
Hide Description Each relevant clinical characteristic will be recorded by the use of tables and/or graphs. The number and percentage of patients treated, and the primary reason for discontinuation will be displayed. Demographic variables (such as age) and baseline characteristics will be summarized by descriptive statistics. Compliance with pembrolizumab administration will be measured by patients: 1) receiving unscheduled study agent infusions/injections; 2) missing an infusion/injection. Numbers and percentages of patients and infusion/injection visits with any deviation in these measures will be reported.
Time Frame Baseline up to 2 years
Outcome Measure Data Not Reported
Time Frame From the time participants signed consent form through 30 days following cessation of treatment .
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Pembrolizumab)
Hide Arm/Group Description

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Pembrolizumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

All-Cause Mortality
Treatment (Pembrolizumab)
Affected / at Risk (%)
Total   2/5 (40.00%)    
Hide Serious Adverse Events
Treatment (Pembrolizumab)
Affected / at Risk (%) # Events
Total   3/5 (60.00%)    
Gastrointestinal disorders   
Lower GI Hemorrhage   1/5 (20.00%)  1
Small bowel obstruction   1/5 (20.00%)  1
Perforate diverticulitis   1/5 (20.00%)  1
Investigations   
Increased Creatinine   1/5 (20.00%)  1
INR Increased   1/5 (20.00%)  1
Blood bilirubin increased   1/5 (20.00%)  1
Metabolism and nutrition disorders   
Hyperkalemia   1/5 (20.00%)  1
hyperglycemia   1/5 (20.00%)  1
Musculoskeletal and connective tissue disorders   
Muscle weakness   1/5 (20.00%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplassms   1/5 (20.00%)  1
Nervous system disorders   
Encephalopathy   1/5 (20.00%)  1
Renal and urinary disorders   
Acute Kidney Inury   1/5 (20.00%)  1
Respiratory, thoracic and mediastinal disorders   
Pulmonary hypertension   1/5 (20.00%)  1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment (Pembrolizumab)
Affected / at Risk (%) # Events
Total   4/5 (80.00%)    
Blood and lymphatic system disorders   
Anemia   2/5 (40.00%)  5
Endocrine disorders   
Hypothyroidism   1/5 (20.00%)  1
Eye disorders   
Dry Eye   1/5 (20.00%)  1
Eye pain   1/5 (20.00%)  1
Retinal vascular disorder   1/5 (20.00%)  1
Gastrointestinal disorders   
Nausea   2/5 (40.00%)  3
Abdominal pain   1/5 (20.00%)  1
Bloating   1/5 (20.00%)  1
Constipation   1/5 (20.00%)  2
Dry mouth   1/5 (20.00%)  1
Ileus   1/5 (20.00%)  1
Vomiting   1/5 (20.00%)  2
General disorders   
Fatigue   3/5 (60.00%)  5
Limb edema   1/5 (20.00%)  2
Pain   1/5 (20.00%)  1
Infections and infestations   
Upper respiratory infection   1/5 (20.00%)  2
Urinary tract infection   1/5 (20.00%)  1
Injury, poisoning and procedural complications   
Bruising   1/5 (20.00%)  2
Investigations   
Aspartate aminotransferase increased   2/5 (40.00%)  7
Alanine aminotransferase increased   1/5 (20.00%)  2
Alkaline phosphatase increased   1/5 (20.00%)  1
Metabolism and nutrition disorders   
Hyponatremia   2/5 (40.00%)  5
Hyperglycemia   2/5 (40.00%)  4
Hyperkalemia   1/5 (20.00%)  4
Anorexia   1/5 (20.00%)  1
Hypercalcemia   1/5 (20.00%)  1
Hypermagnesemia   1/5 (20.00%)  2
Hyperuricemia   1/5 (20.00%)  1
Hypoalbuminemia   1/5 (20.00%)  2
Hypocalcemia   1/5 (20.00%)  2
Musculoskeletal and connective tissue disorders   
Arthritis   1/5 (20.00%)  1
Back pain   1/5 (20.00%)  1
Pain in extremity   1/5 (20.00%)  1
Nervous system disorders   
Dysgeusia   1/5 (20.00%)  1
Peripheral sensory neuropathy   1/5 (20.00%)  1
Psychiatric disorders   
Insomnia   1/5 (20.00%)  1
Skin and subcutaneous tissue disorders   
Pruritus   1/5 (20.00%)  1
Rash maculo-papular   1/5 (20.00%)  1
Skin hypopigmentation   1/5 (20.00%)  1
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Principal Investigator
Organization: Vanderbilt-Ingram Cancer Center
Phone: 615-936-7423
EMail: douglas.b.johnson@vanderbilt.edu
Layout table for additonal information
Responsible Party: Douglas Johnson, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT02359851    
Other Study ID Numbers: VICC MEL1486
NCI-2015-00020 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA068485 ( U.S. NIH Grant/Contract )
First Submitted: February 4, 2015
First Posted: February 10, 2015
Results First Submitted: February 7, 2018
Results First Posted: April 24, 2018
Last Update Posted: September 18, 2019