Pembrolizumab in Treating Patients With Advanced Uveal Melanoma

NCT02359851 | Terminated Phase 2 Results DMC

• 3 other identifiers: VICC MEL1486NCI-2015-00020P30CA068485
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

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.

Conditions

Stage IIIA Uveal Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Uveal Melanoma; Stage IV Uveal Melanoma

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  Interval between the first dose of pembrolizumab and death for any reason, assessed up to 3 years

• Response Duration

  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

  Up to 30 days after the last dose of trial treatment

Other Outcomes (3)

• Changes in GNAQ/GNA11 Mutation Status on Each Patient Per Institutional Protocol

  Baseline up to 2 years

• Change in PD-L1 Expression Status on Archival or Fresh Tissue From All Patients and Correlate With ORR

  Baseline up to 2 years

• Changes in Molecular Characteristics of Uveal Melanoma When Treated With Pembrolizumab

  Baseline up to 2 years

Study Arms (1)

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.

Biological: Pembrolizumab; Other: Laboratory Biomarker Analysis

Interventions

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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 a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 30787124 DERIVED

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

MeSH Terms

Conditions

Uveal Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Results Point of Contact

• Title: Principal Investigator
• Organization: Vanderbilt-Ingram Cancer Center

douglas.b.johnson@vanderbilt.edu

615-936-7423

Study Officials

• Douglas Johnson

  Vanderbilt-Ingram Cancer Center

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 4, 2015
• First Posted: February 10, 2015
• Study Start: May 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: August 27, 2019
• Last Updated: September 18, 2019
• Results First Posted: April 24, 2018

Record last verified: 2019-09

Locations

US (2)