Pembrolizumab in Treating Patients With Advanced Uveal Melanoma
Primary Purpose
Stage IIIA Uveal Melanoma, Stage IIIB Uveal Melanoma, Stage IIIC Uveal Melanoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Laboratory Biomarker Analysis
Sponsored by
About this trial
This is an interventional treatment trial for Stage IIIA Uveal Melanoma
Eligibility Criteria
Inclusion Criteria:
- Be willing and able to provide written informed consent/assent for the trial
- Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Histologic confirmation of advanced (metastatic or unresectable) uveal melanoma. If uveal melanoma has been diagnosed clinically and/or by gene expression profiling, patients may be included following discussion with the principal investigator.
- Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Platelets >= 100,000/mcL
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
- Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN; creatinine clearance should be calculated per institutional standard
- Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male subjects should 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
Exclusion Criteria:
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
- Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
- Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the study
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-cluster of differentiation (CD)137; patients who received anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) (ipilimumab, tremelimumab) will NOT be excluded and are eligible for inclusion
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- Has received a live vaccine within 30 days prior to the first dose of trial treatment
Sites / Locations
- University of Chicago
- Vanderbilt-Ingram Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (pembrolizumab)
Arm 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.
Outcomes
Primary Outcome Measures
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)
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.
Secondary Outcome Measures
Progression-Free Survival (PFS) Defined as Time From Treatment to Progression Defined by RECIST1.1 Criteria or Death.
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.
Overall Survival (OS) Defined as Number of Patients Surviving up to 3 Years.
The Kaplan-Meier method will be used to estimate the overall survival. Median survival and its 95% confidence interval will be estimated and reported.
Response Duration
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.
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
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.
Full Information
NCT ID
NCT02359851
First Posted
February 4, 2015
Last Updated
September 3, 2019
Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02359851
Brief Title
Pembrolizumab in Treating Patients With Advanced Uveal Melanoma
Official Title
A Multicenter Phase II Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) in Patients With Advanced Uveal Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
May 2015 (undefined)
Primary Completion Date
May 2017 (Actual)
Study Completion Date
August 27, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This phase II trial studies how well pembrolizumab works in treating patients with uveal melanoma that has spread to other places in the body and usually cannot be cured or controlled with treatment. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells.
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate objective response rate (ORR) in patients with advanced uveal melanoma receiving pembrolizumab.
SECONDARY OBJECTIVES:
I. To evaluate progression-free survival (PFS) in patients with advanced uveal melanoma receiving pembrolizumab.
II. To evaluate safety, tolerability and adverse experience profile of pembrolizumab in uveal melanoma.
III. To evaluate overall survival (OS) in patients with advanced uveal melanoma receiving pembrolizumab.
TERTIARY OBJECTIVES:
I. To evaluate objective response rate (ORR; complete response + partial response) in patients with advanced uveal melanoma receiving pembrolizumab as stratified by programmed cell death-ligand 1 (PD-L1) expression and guanine nucleotide-binding protein (GNA)Q/GNA11 mutation status.
II. To evaluate ORR in patients previously treated with ipilimumab or with mitogen-activated protein kinase kinase (MEK) inhibitors.
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IIIA Uveal Melanoma, Stage IIIB Uveal Melanoma, Stage IIIC Uveal Melanoma, Stage IV Uveal 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
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (pembrolizumab)
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, Lambrolizumab, MK-3475, SCH 900475
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
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)
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
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS) Defined as Time From Treatment to Progression Defined by RECIST1.1 Criteria or Death.
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.
Title
Overall Survival (OS) Defined as Number of Patients Surviving up to 3 Years.
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
Title
Response Duration
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
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
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
Other Pre-specified Outcome Measures:
Title
Changes in GNAQ/GNA11 Mutation Status on Each Patient Per Institutional Protocol
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
Title
Change in PD-L1 Expression Status on Archival or Fresh Tissue From All Patients and Correlate With ORR
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
Title
Changes in Molecular Characteristics of Uveal Melanoma When Treated With Pembrolizumab
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be willing and able to provide written informed consent/assent for the trial
Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Histologic confirmation of advanced (metastatic or unresectable) uveal melanoma. If uveal melanoma has been diagnosed clinically and/or by gene expression profiling, patients may be included following discussion with the principal investigator.
Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
Absolute neutrophil count (ANC) >= 1,500/mcL
Platelets >= 100,000/mcL
Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN; creatinine clearance should be calculated per institutional standard
Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
Male subjects should 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
Exclusion Criteria:
Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the study
Has evidence of interstitial lung disease or active, non-infectious pneumonitis
Has an active infection requiring systemic therapy
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-cluster of differentiation (CD)137; patients who received anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) (ipilimumab, tremelimumab) will NOT be excluded and are eligible for inclusion
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
Has received a live vaccine within 30 days prior to the first dose of trial treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas Johnson
Organizational Affiliation
Vanderbilt-Ingram Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30787124
Citation
Johnson DB, Bao R, Ancell KK, Daniels AB, Wallace D, Sosman JA, Luke JJ. Response to Anti-PD-1 in Uveal Melanoma Without High-Volume Liver Metastasis. J Natl Compr Canc Netw. 2019 Feb;17(2):114-117. doi: 10.6004/jnccn.2018.7070.
Results Reference
derived
Links:
URL
http://vicc.org/ct/
Description
Vanderbilt-Ingram Cancer Center, Find a Clinical Trial
Learn more about this trial
Pembrolizumab in Treating Patients With Advanced Uveal Melanoma
We'll reach out to this number within 24 hrs