Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma

NCT01979523 | Active Not Recruiting Phase 2 Results

• 5 other identifiers: NCI-2013-0209113-1449445N01CM00039P30CA008748
• Study Type: interventional
• Target: 42
• Locations: 3 countries
• Sites: 7

Brief Summary

This randomized phase II trial studies how well trametinib with or without Akt inhibitor GSK2141795 (GSK2141795) works in treating patients with uveal melanoma that has spread to other parts of the body (metastatic). Trametinib and GSK2141795 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trametinib is more effective with or without GSK2141795 in treating patients with metastatic uveal melanoma.

Conditions

Stage IV Uveal Melanoma AJCC v7; Recurrent Uveal Melanoma

Outcome Measures

Primary Outcomes (1)

• Time to Progression (Progression-free Survival [PFS]), Defined From the Date of Randomization to the Date of Documented Progression or Death Per RECIST

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  from randomization to the earlier date of objective disease progression or death

Secondary Outcomes (3)

• Number of Participants With Toxicity, Graded According to the National Cancer Institute CTCAE v4.0, Who Were Treated and Did Not Withdraw Consent

  From date of randomization until the date of death from any cause or 4 weeks from last treatment of the initial treatment assignment, whichever came first, assessed up to 12 months

• Overall Survival (OS) Per RECIST Criteria

  up to 36 months

• Response Rate (Complete Response+ Partial Response) Using the RECIST Criteria

  From date of randomization until the date of death from any cause or 4 weeks from last treatment of the initial treatment assignment, whichever came first, assessed up to 12 months

Other Outcomes (4)

• Change in Apoptosis in Paired Samples as Assessed by Caspase 3 Cleavage

  Baseline to 4 weeks from last treatment

• Change in Suppression of Phosphorylated (p)-ERK, AKT, and Cyclin-D1

  Baseline to 4 weeks from last treatment

• Circulating Tumor DNA Levels

  Up to 4 weeks from last treatment

Study Arms (2)

Arm A (trametinib)

EXPERIMENTAL

Patients receive trametinib PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who experience objective disease progression may crossover to Arm B. (no patients will be enrolled to Arm B or Crossover therapy as of 11/6/2015)

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Trametinib

Arm B (trametinib, Akt inhibitor GSK2141795)

EXPERIMENTAL

Patients receive trametinib PO QD and Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Trametinib; Drug: Uprosertib

Interventions

Trametinib DRUG

Given PO

Also known as: GSK 1120212, GSK 212, GSK-1120212, GSK-212, GSK1120212, GSK212, JTP 74057, JTP-74057, JTP74057, MEK Inhibitor GSK1120212

Arm A (trametinib); Arm B (trametinib, Akt inhibitor GSK2141795)

Uprosertib DRUG

Given PO

Also known as: GSK2141795, Oral Akt Inhibitor GSK2141795

Arm B (trametinib, Akt inhibitor GSK2141795)

Pharmacological Study OTHER

Correlative studies

Arm A (trametinib); Arm B (trametinib, Akt inhibitor GSK2141795)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (trametinib); Arm B (trametinib, Akt inhibitor GSK2141795)

Eligibility Criteria

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

You may qualify if:

• Patients must have metastatic histologically or cytologically confirmed uveal melanoma; if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma; pathologic confirmation of metastatic disease will be performed at Memorial Sloan Kettering (MSK) or at a participating site
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
• Patients may not have received prior systemic or hepatic directed infusional/embolization therapies for advanced uveal melanoma; local therapies such as radiofrequency ablation or cryotherapy for metastatic disease are permitted but must have been performed at least 21 days prior to initiation of study therapy; lesions treated with local modalities such as radiofrequency ablation or cryotherapy may not be used as target lesions unless they demonstrate growth over a minimum of 3 months on subsequent imaging studies
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Life expectancy of greater than 3 months
• Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) version (v)4 grade =\< 1 (except alopecia) at the time of randomization and crossover
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9.0 g/dL (not requiring transfusions within the past 2 weeks)
• Total bilirubin =\< 1.5 x institutional upper limit of normal; Note: patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional upper limit of normal for patients with no concurrent liver metastases, OR =\< 2.5 x institutional upper limit of normal for patients with concurrent liver metastases
• Creatinine =\< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) \>= 50 mL/min OR 24-hour urine creatinine clearance \>= 50 mL/min
• Left ventricular ejection fraction \>= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA)

You may not qualify if:

• History of another malignancy except for those who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies not requiring active therapy, are eligible; consult the study MSK Principal Investigator or the Cancer Therapy Evaluation Program (CTEP) Medical Monitor if unsure whether second malignancies meet the requirements specified above
• History of interstitial lung disease or pneumonitis
• Any major surgery or extensive radiotherapy within 21 days prior to randomization and crossover
• Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib alone or with GSK2141795 and during the study
• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression; treated brain metastases must have been stable for at least 1 month
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, GSK2141795, or excipients or to dimethyl sulfoxide (DMSO)
• Current use of a prohibited medication
• History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) in the eye unaffected by uveal melanoma
• Patients with abnormal fasting glucose values (values \> upper limit of normal \[ULN\] or \< LLN) at screening will be excluded; in addition, patients with type 1 diabetes will also be excluded; however, patients with type 2 diabetes will be allowed if diagnosed \>= 6 months prior to enrollment, and if presenting with a normal fasting glucose value and a regular hemoglobin A1C (HbA1C) =\< 8% at screening
• History or evidence of cardiovascular risk including any of the following:
• Left ventricular ejection fraction (LVEF) \< LLN
• A QT interval corrected for heart rate using the Bazett's formula QTcB \>= 480 msec
• History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for \> 30 days prior to randomization are eligible)
• History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization
• History or evidence of current \>= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Institut Curie Paris

Paris, 75005, France

Location

The University of Liverpool

Liverpool, L69 3GA, United Kingdom

Location

MeSH Terms

Conditions

Uveal Melanoma

Interventions

trametinib; omipalisib; GSK2141795

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: Dr. Alexander Shoushtari
• Organization: Memorial Sloan Kettering Cancer Center

shoushta@mskcc.org

646-888-4161

Study Officials

• Alexander N Shoushtari

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2013
• First Posted: November 8, 2013
• Study Start: November 21, 2013
• Primary Completion: September 1, 2017
• Study Completion (Estimated): July 2, 2026
• Last Updated: April 13, 2026
• Results First Posted: February 24, 2020

Record last verified: 2026-01

Locations

FR (1); US (5); GB (1)