Stage IIIA Uveal MelanomaPhase 2NCT02359851
Pembrolizumab in Treating Patients With Advanced Uveal Melanoma
A Phase 2 study testing Pembrolizumab and Laboratory Biomarker Analysis in people with Stage IIIA Uveal Melanoma and Stage IIIB Uveal Melanoma, run by Vanderbilt-Ingram Cancer Center at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IIIA Uveal Melanoma, Stage IIIB Uveal Melanoma, Stage IIIC Uveal Melanoma
- What is being tested?
- Pembrolizumab and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2015to 27 Aug 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Chicago
Chicago, Illinois, 60637
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
Official title: A Multicenter Phase II Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) in Patients With Advanced Uveal Melanoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate objective response rate (ORR) in patients with advanced uveal melanoma receiving pembrolizumab.
SECONDARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Stage IIIA Uveal Melanoma, Stage IIIB Uveal Melanoma, Stage IIIC Uveal Melanoma, Stage IV Uveal Melanoma
- Being tested
- Pembrolizumab, Laboratory Biomarker Analysis
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pembrolizumab) | Experimental | 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. Receives: Biological: Pembrolizumab; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 3 years
Secondary outcomes (4)
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.
Measured: Time from the first dose of pembrolizumab to progression, assessed up to 3 years.
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.
Measured: Interval between the first dose of pembrolizumab and death for any reason, assessed up to 3 years
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.
Measured: Up to 3 years
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.
Measured: Up to 30 days after the last dose of trial treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2015 (estimated)
- Study startMay 2015
- Primary completionMay 2017
- Study completion27 Aug 2019
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stage IIIA Uveal MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Douglas Johnson, Vanderbilt-Ingram Cancer Center
- Investigators
- Douglas Johnson, Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02359851
- Sponsor's protocol ID
- VICC MEL1486
- Other IDs
- NCI-2015-00020, P30CA068485
- Status last verified
- Sep 2019
- First submitted
- 4 Feb 2015
- Last updated
- 18 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30787124
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase II Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) in Patients With Advanced Uveal Melanoma
- ClinicalTrials.gov ID
- NCT02359851
- Acronym / sponsor ID
- VICC MEL1486
- Conditions
- Stage IIIA Uveal Melanoma, Stage IIIB Uveal Melanoma, Stage IIIC Uveal Melanoma, Stage IV Uveal Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2015
- Primary completion
- May 2017 (actual)
- Study completion
- 27 Aug 2019 (actual)
- First posted
- 10 Feb 2015 (estimated)
- Results
- Posted 24 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To evaluate objective response rate (ORR) in patients with advanced uveal melanoma receiving pembrolizumab.
SECONDARY OBJECTIVES:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pembrolizumab) | Experimental | Biological: Pembrolizumab, Other: Laboratory Biomarker AnalysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (18 listed)
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Treatment (pembrolizumab) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pembrolizumab) |
Primary outcome
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)
Time frame: Up to 3 years
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.
4 secondary outcomes
Progression-Free Survival (PFS) Defined as Time From Treatment to Progression Defined by RECIST1.1 Criteria or Death.
Time frame: Time from the first dose of pembrolizumab to progression, assessed up to 3 years.
Overall Survival (OS) Defined as Number of Patients Surviving up to 3 Years.
Time frame: Interval between the first dose of pembrolizumab and death for any reason, assessed up to 3 years
Response Duration
Time frame: Up to 3 years
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
Time frame: Up to 30 days after the last dose of trial treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30787124Johnson 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.
- Vanderbilt-Ingram Cancer Center, Find a Clinical TrialLink provided by the sponsor.
Related trials for Stage IIIA Uveal Melanoma
Active, not recruitingPhase 2
Sunitinib Malate or Valproic Acid in Preventing Metastasis in Patients With High-Risk Uveal Melanoma
Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Douglas Johnson principal investigator
Vanderbilt-Ingram Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Laboratory Biomarker Analysis in people with Stage IIIA Uveal Melanoma and Stage IIIB Uveal Melanoma, run by Vanderbilt-Ingram Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02359851, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2019.