Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Eye Diseases

Rare Diseases

Recurrence

Melanoma

Uveal Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Eye Neoplasms

Uveal Diseases

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Trametinib

Protein Kinase Inhibitors

Enzyme Inhibitors

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)

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.

Laboratory Biomarker Analysis

Pharmacological Study

Uprosertib

Alexander Shoushtari

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.

PRIMARY OBJECTIVES:

I. To compare progression-free survival between those treated with trametinib alone and those treated with the combination of trametinib and GSK2141795.

SECONDARY OBJECTIVES:

I. To compare overall survival between those treated with trametinib alone and those treated with the combination of trametinib and GSK2141795.

II. To compare the overall response rate between those treated with trametinib alone and those treated with the combination of trametinib and GSK2141795.

III. To compare the safety and toxicity between those treated with trametinib alone and those treated with the combination of trametinib and GSK2141795.

TERTIARY OBJECTIVES:

I. To assess clinical outcomes (response rate, progression-free and overall survival) with trametinib and GSK2141795 after progression on trametinib.

II. To assess toxicity with trametinib and GSK2141795 after progression on trametinib.

III. To correlate clinical outcome with Gnaq/11 mutational status. IV. To assess the pharmacodynamic effects of trametinib alone and with GSK2141795, and utilize whole-transcriptome and reverse phase protein array to identify markers of sensitivity and primary resistance to trametinib alone and with GSK2141795.

V. To assess for changes in circulating tumor deoxyribonucleic acid (DNA) with therapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive trametinib orally (PO) once daily (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)

ARM B: 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.

After completion of study treatment, patients are followed up for 4 weeks and then every 12 weeks thereafter.

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

A Randomized Two-Arm Phase II Study of Trametinib Alone and in Combination With GSK2141795 in Patients With Advanced Uveal Melanoma

Association between suppression and response to treatment will be assessed using Fisher's exact test.

The numeric data will be summarized by clinical response.

Clinical response will be associated with Gnaq/11 mutational status using Wilcoxon rank sum test.

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.

Graded according to the National Cancer Institute CTCAE v4.0. Please see AE/SAE Section for specifics.

OS curves will be generated using Kaplan-Meier methodology.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD); PD, 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; Complete Response (CR), Disappearance of all target lesions.

National Cancer Institute (NCI)

AE's and SAE's for Arm A, Arm B, and the crossover group were collected.

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)

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Trametinib: Given PO

Arm A (Trametinib)

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.

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Trametinib: Given PO

Uprosertib: Given PO

Arm B (Trametinib, Akt Inhibitor GSK2141795)

Participants had progression of disease on Arm A and were then treated on Arm B.

Crossover Arm

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Alexander Shoushtari

This assessment corresponds to the participants' initial treatment assignment.

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

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

Overall Survival (OS) Per RECIST Criteria

Partial Response

Progression of Disease

Stable Disease

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

The size of the cores from the acquired samples in almost all participants were small and the quality was insufficient to analyze across the sample set.

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

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

Data were not analyzed due to lack of funding.

Circulating Tumor DNA Levels

Analysis across the sample set unable to be completed due to patient-specific issues (participants skipped biopsy for safety, insufficient cores for extra DNA extraction)

Gnaq/11 Mutational Status

Overall Study

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Patients receive trametinib orally PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or who achieve less than PR after 4 courses may also receive Akt inhibitor GSK2141795 PO daily on days 1-28.

Suzanne Trudel

This phase II trial studies how well trametinib and Akt inhibitor GSK2141795 work in treating patients with multiple myeloma that has come back (relapsed) or that does not respond to treatment (refractory). Trametinib and Akt inhibitor GSK2141795 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the antitumor activity of trametinib determined by overall response rate (ORR) in patients that are stratified into groups based on: biomarker positive (neuroblastoma RAS viral \[v-ras\] oncogene homolog \[NRAS\], v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog \[KRAS\], v-raf murine sarcoma viral oncogene homolog B1 \[BRAF\] mutated) and biomarker negative (without NRAS, KRAS, BRAF mutation).

SECONDARY OBJECTIVES:

I. To evaluate progression free survival (PFS) and duration of response (DOR) in the two stratified groups.

II. To document ORR after the addition of GSK2141795 (Akt inhibitor GSK2141795) to trametinib in patients who have developed progressive disease or have achieved less than a partial response (PR) after 4 cycles of treatment.

III. To evaluate PFS and DOR in patients receiving trametinib plus GSK2141795. IV. To evaluate the safety profile of trametinib with and without GSK2141795.

TERTIARY OBJECTIVES:

I. To explore the relationship between clinical response and pharmacodynamic (PD) markers.

II. To explore the relationship between v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF) expression as determined by quantitative polymerase chain reaction (qPCR), chromosomal abnormalities detected by florescence in situ hybridization (FISH), and clinical response.

III. To explore the role of integrin beta7 as a biomarker of MAF expression. IV. To explore the relationship between objective clinical response as well as progressive disease and the tumor mutational profile.

V. To explore mechanism of phosphatidylinositol 3 kinase (PI3K)/v-akt Murine Thymoma Viral Oncogene Homolog 1 (AKT) and retrovirus-associated deoxyribonucleic acid (DNA) sequence (RAS)-mitogen-activated protein kinase kinase (MEK)-mitogen-activated protein kinase 1 (ERK) activation and correlate these with clinical response and PD markers.

IV. To explore the feasibility of extracting circulating free tumor DNA (cfDNA) from peripheral blood and detecting RAS and RAF mutations using cfDNA.

OUTLINE:

Patients receive trametinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or who achieve less than PR after 4 courses may also receive Akt inhibitor GSK2141795 PO daily on days 1-28.

After completion of study treatment, patients are followed up for 4 weeks.

Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Relapsed or Refractory Multiple Myeloma

A Phase 2 Study of Sequential Trametinib and GSK2141795 in Relapsed or Refractory Multiple Myeloma

Analyses will be descriptively summarized.

Ultra-deep sequencing will be performed on cfDNA to assess the feasibility of detecting mutations of NRAS, KRAS and BRAF from peripheral blood samples.

"Per International Myeloma Working Group (IMWG) Criteria: Complete Response (CR), Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow; Partial Response (PR), \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h; Overall Response (OR) = CR + PR."

Summarized for each cohort using the Kaplan-Meier method, from the date of start of treatment to the date of documented progression (based on IMWG criteria) or death due to any cause, assessed every 4 weeks

Summarized for each cohort using the Kaplan-Meier method.

Reported by type, frequency, and severity.

Adverse events collected as per protocol using CTCAE version 4.0

Patients receive trametinib orally PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or who achieve less than PR after 4 courses may also receive Akt inhibitor GSK2141795 PO daily on days 1-28.

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Trametinib: Given PO

Uprosertib: Given PO

Treatment (Trametinib, Akt Inhibitor GSK2141795)

Age, Categorical

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Canada

Dr. Suzanna Trudel

Patients receive trametinib orally PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment (Trametinib)

Patients who develop progressive disease on trametinib monotherapy or achieve less then a PR after 4 cycles of treatment will have the option to continue on trametinib with the addition of GSK2141795

ORR Evidenced by Confirmed Response Rate, Defined as Number of Patients With Partial Response or Better by International Myeloma Working Group (IMWG) Criteria Divided by the Number of Patients in the Applicable Group (Biomarker Positive or Negative)

Note: 25 patients enrolled, however, one patient unevaluable was not included in analysis

Not reported. Data were not collected and not analyzed for this outcome measure.

DOR (Duration of Response)

Trametinib monotherapy arm not applicable for this outcome measure

ORR After the Addition of AKT Inhibitor GSK2141795 to Trametinib in Patients Who Have Developed Progressive Disease or Have Achieved Less Than a PR

Incidence of Adverse Event Reactions Reported According to CTCAE v4.0

Pharmacodynamic Markers of Trametinib

Chromosomal Abnormalities as Determined by FISH

Tumor Mutational Profile by Next Generation Sequencing

Change in RAS-MEK-ERK Activation Determined by Phospho-flow Cytometry and RPPA (Reversal Phase Protein Arrays)

Ultra-deep sequencing will be performed on cfDNA to assess the feasibility of detecting mutations of KRAS from peripheral blood samples.

Detection of KRAS Mutations Using cfDNA

Ultra-deep sequencing will be performed on cfDNA to assess the feasibility of detecting mutations of NRAS from peripheral blood samples.

Detection of NRAS Mutations Using cfDNA

Ultra-deep sequencing will be performed on cfDNA to assess the feasibility of detecting mutations of BRAF from peripheral blood samples.

Detection of BRAF Mutations Using cfDNA

64 cfDNA specimens from 53 Myeloma patients including 13 patients from this trial that were included in this analysis

Detection of RAS and RAF Mutations Using cfDNA

Patients receive trametinib orally PO QD (once daily) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or who achieve less than PR after 4 courses may also receive Akt inhibitor GSK2141795 PO daily on days 1-28.

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Trametinib: Given PO

Uprosertib: Given PO

Melanoma, Cutaneous Malignant

Dabrafenib

Dimethyl Sulfoxide

Protective Agents

Antioxidants

Dabrafenib mesylate and uprosertib (Phase I): Patients receive dabrafenib PO BID and uprosertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, MRI, and blood sample collection throughout trial. Patients may also undergo a biopsy throughout the trial.

Dabrafenib mesylate, trametinib dimethyl sulfoxide, and uprosertib (Phase I and Phase II): Patients receive dabrafenib PO BID, trametinib PO QD, and uprosertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, MRI, and blood sample collection throughout trial. Patients may also undergo a biopsy throughout the trial.

Biopsy

Biospecimen Collection

Computed Tomography

Dabrafenib Mesylate

Magnetic Resonance Imaging

Trametinib Dimethyl Sulfoxide

Antoni Ribas

This phase I/II trial studies the side effects and the best dose of uprosertib when given together with dabrafenib and trametinib and to see how well they work in treating patients with stage IIIC-IV cancer. Uprosertib, dabrafenib, and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving uprosertib with dabrafenib and trametinib may be a better treatment for cancer.

PRIMARY OBJECTIVES:

I. To assess the safety of dabrafenib mesylate (dabrafenib) in combination with uprosertib (GSK2141795) and select the optimal dose of GSK2141795 for the phase II portion in patients with BRAF mutant cancer. (Effective November 15, 2014, this trial will not proceed to the phase II study of dabrafenib and GSK2141795, but will move to an evaluation of triple therapy). (Phase I) II. To assess the safety of dabrafenib and trametinib dimethyl sulfoxide (trametinib) and GSK2141795 in combination and select the optimal dose of the combination for the phase II portion in patients with BRAF mutant cancer. (Phase I) III. To evaluate the objective response rate (confirmed and unconfirmed, complete and partial responses) in patients with BRAF\^V600 mutant metastatic melanoma who have previously progressed on BRAF\^V600 inhibitor-based therapy (BRAFi), or BRAFi + MEK inhibitor-based therapy (MEKi). (Phase II)

SECONDARY OBJECTIVES:

I. To estimate overall survival and progression-free survival. II. To assess the toxicity profile of the recommended phase II dose. III. To assess response (complete and partial, confirmed and unconfirmed) of patients enrolled on each phase I portion).

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To explore the molecular mechanisms of acquired resistance to BRAF inhibitor therapy using available biopsies of lesions that progressed during prior BRAF inhibitor-based therapy.

II. To explore potential drug-drug interactions between dabrafenib and GSK2141795 leading to changes in the expected exposure with either agent compared to prior experience. (Phase I)

OUTLINE: This is a phase I, dose-escalation study of uprosertib followed by a phase II study. Dose escalation of dabrafenib mesylate, trametinib dimethyl sulfoxide, and uprosertib will be initiated after completion of the dabrafenib + uprosertib phase I dose escalation.

Dabrafenib mesylate and uprosertib (Phase I): Patients receive dabrafenib orally (PO) twice daily (BID) and uprosertib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a computed tomography (CT) scan, magnetic resonance imaging (MRI), and blood sample collection throughout trial. Patients may also undergo a biopsy throughout the trial.

Dabrafenib mesylate, trametinib dimethyl sulfoxide, and uprosertib (Phase I and Phase II): Patients receive dabrafenib PO BID, trametinib PO QD, and uprosertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, magnetic MRI, and blood sample collection throughout trial. Patients may also undergo a biopsy throughout the trial.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.

Uprosertib, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer

Phase I/II Study of the Safety and Efficacy of the AKT Inhibitor GSK2141795 in Combination With Dabrafenib and Trametinib in Patients With BRAF Mutant Cancer

For binary markers, the prevalence will be able to be estimated and exact binomial confidence interval will be calculated. The association between these categorical markers and clinical outcomes will be explored in a preliminary manner, using Fisher's exact test to compare response and a logrank test to compare Kaplan-Meier estimates of overall survival and progression free survival between marker positive and marker negative groups.

MTD was evaluated by testing increasing doses up to 75 mg once a day, given in combination with dabrafenib dosed at 150 mg twice daily. MTD reflects the highest dose that did not cause a DLT. DLTs were defined as treatment regimen related: febrile neutropenia; Grade 4 neutropenia lasting more than 7 days; Grade 4 platelet count decrease; Grade 3-4 rash, fever, or hyperglycemia \> 14 days, e) Grade 3-4 non-hematologic adverse events lasting greater than 7 days. Adverse events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

MTD was evaluated by testing increasing doses up to 75 mg once a day, given in combination with dabrafenib dosed at 150 mg twice daily and trametinib at either 1.5 mg or 2 mg once a day. MTD reflects the highest dose that did not cause a dose-limiting toxicity (DLT). DLTs were defined as treatment regimen related: febrile neutropenia; Grade 4 neutropenia lasting more than 7 days; Grade 4 platelet count decrease; Grade 3-4 rash, fever, or hyperglycemia \> 14 days, e) Grade 3-4 non-hematologic adverse events lasting greater than 7 days. Adverse events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Note: MTD for the triplet regimen could not be determined due to the end of supply of the study drug. Number reported is the maximum dose of GSK2141795 that was assessed in combination with 150 mg Dabrafenib and 2 mg trametinib.

All measurable lesions up to a maximum of 2 lesions per organ 5 lesions in total, representative of all involved organs, were identified as target lesions at baseline. All other lesions (or sites of disease) were identified as non-target lesions.

Complete Response (CR): Complete disappearance of all target and nontarget lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to \< 1.0 cm.

Partial Response (PR): \<= 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions.

Unconfirmed CR: One objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR.

Unconfirmed PR: One objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

GlaxoSmithKline

Novartis Pharmaceuticals

Doublet regimen cohort 1: participants were given 150 mg of dabrafenib twice daily and 50 mg of GK2141795 once daily.

Dabrafenib + GSK2141795 50 mg

Doublet regimen cohort 2: participants were given 150 mg of dabrafenib twice daily and 75 mg of GK2141795 once daily.

Dabrafenib + GSK2141795 75 mg

Triplet regimen cohort 1: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 25 mg of GK2141795 once daily.

Dabrafenib + Trametinib 1.5 mg + GSK2141795 25 mg

Triplet regimen cohort 2: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 50 mg of GK2141795 once daily.

Dabrafenib + Trametinib 1.5 mg + GSK2141795 50 mg

Triplet regimen cohort 3: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 75 mg of GK2141795 once daily.

Dabrafenib + Trametinib 1.5 mg + GSK2141795 75 mg

Triplet regimen cohort 4: participants were given 150 mg of dabrafenib twice daily, 2 mg of trametinib and 75 mg of GK2141795 once daily.

Dabrafenib + Trametinib 2 mg + GSK2141795 75 mg

Doublet regimen cohort 1: participants were given 150 mg of dabrafenib twice daily and 50 mg of GSK2141795 once daily.

Doublet regimen cohort 2: participants were given 150 mg of dabrafenib twice daily and 75 mg of GSK2141795 once daily

Triplet regimen cohort 1: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 25mg of GSK2141795 once daily.

Dabrafenib + Trametinib 1.5mg + GSK2141795 25mg

Triplet regimen cohort 2: participants were given 150mg of dabrafenib twice daily, 1.5mg of trametinib and 50mg of GSK2141795 once daily

Dabrafenib + Trametinib 1.5mg + GSK2141795 50mg

Triplet regimen cohort 3: participants were given 150 mg of dabrafenib twice daily, 1.5 mg of trametinib and 75mg of GSK2141795 once daily.

Dabrafenib + Trametinib 1.5mg + GSK2141795 75mg

Triplet regimen cohort 4: participants were given 150 mg of dabrafenib twice daily, 2 mg of trametinib and 75 mg of GSK2141795 once daily.

Dabrafenib + Trametinib 2.0mg + GSK2141795 75mg

Prior BRAF inhibitor

Type of cancer

Total number of eligible and evaluable patients i.e. patients that received at least one dose of protocol therapy.

Melanoma Statistician

All analyzable patients who experienced a dose limiting toxicity OR at least received GSK2141795 for 11 days in Cycle 1 and dabrafenib for 28 days in cycles 1 and 2 OR at least received GSK2141795 for 11 days in Cycle 1 and 50% of dabrafenib in Cycle 1

Phase 1 Doublet Regimen

Eligible, analyzable and evaluable participants that were assessed for DLT. In the Dabrafenib + GSK2141795 75 mg arm, 1 participant was ineligible, 3 participants were not analyzable, and 1 participant did not satisfy protocol-specified criteria for DLT evaluation. These patients were excluded from DLT analysis.

Maximum-tolerated Dose (MTD) of Akt Inhibitor GSK2141795 in Combination With Dabrafenib.

All analyzable patients who experienced a dose limiting toxicity OR at least received GSK2141795 for 11 days in Cycle 1 and dabrafenib and trametinib for 28 days each in cycles 1 and 2 OR at least received GSK2141795 for 11 days in Cycle1 and 50% of dabrafenib and trametinib each in Cycle 1

Phase 1 Triplet Regimen

Eligible and evaluable participants that were assessed for DLT. 1 participant in the Dabrafenib + Trametinib 1.5 mg + GSK2141795 25 mg was not eligible. 1 participant in the Dabrafenib + Trametinib 2.0 mg + GSK2141795 75 mg arm did not satisfy protocol-specified criteria for DLT evaluation and was thus excluded.

Maximum-tolerated Dose (MTD) of Akt Inhibitor GSK2141795 in Combination With Dabrafenib and Trametinib.

Patients who received at least one dose of protocol therapy at the Phase I determined MTD.

Dabrafenib + GSK2141795 at MTD

No participants were enrolled to Phase II portion due to the end of the supply of GSK2141795

Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses) as Assessed by RECIST Version 1.1 of the Doublet Regimen GSK2141795 + Dabrafenib at the Phase I Determined MTD. (Phase II)

Dabrafenib + Trametinib + GSK2141795 at MTD

Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses) as Assessed by RECIST Version 1.1 of the Triplet Regimen GSK2141795 + Dabrafenib + Trametinib at the Phase I Determined MTD. (Phase II)

Patients who received at least 1 dose of protocol therapy at the Phase I determined MTD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma	NCT01979523	Recurrent Uveal... Stage IV Uveal ...	Laboratory Biom... Pharmacological... Trametinib Uprosertib	18 Years -	National Cancer Institute (NCI)
Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Relapsed or Refractory Multiple Myeloma	NCT01989598	Recurrent Plasm... Refractory Plas...	Laboratory Biom... Pharmacological... Trametinib Uprosertib	18 Years -	National Cancer Institute (NCI)
Uprosertib, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer	NCT01902173	Hematopoietic a... Locally Advance... Locally Advance... Metastatic Mali... Metastatic Mela... Stage IIIC Cuta... Stage IV Cutane... Unresectable Ma... Unresectable Me...	Biopsy Biospecimen Col... Computed Tomogr... Dabrafenib Mesy... Magnetic Resona... Trametinib Dime... Uprosertib	18 Years -	National Cancer Institute (NCI)
Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Relapsed or Refractory Multiple Myeloma	NCT01989598	Recurrent Plasm... Refractory Plas...	Laboratory Biom... Pharmacological... Trametinib Uprosertib	18 Years -	National Cancer Institute (NCI)
Trametinib With or Without GSK2141795 in Treating Patients With Recurrent or Persistent Endometrial Cancer	NCT01935973	Endometrial Ade... Endometrial Cle... Endometrial Mix... Endometrial Ser... Endometrial Und... Recurrent Uteri...	Laboratory Biom... Trametinib Uprosertib	18 Years -	National Cancer Institute (NCI)
Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma	NCT01979523	Recurrent Uveal... Stage IV Uveal ...	Laboratory Biom... Pharmacological... Trametinib Uprosertib	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for uprosertib

Every month we try and update this database with for uprosertib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for uprosertib

Every month we try and update this database with for uprosertib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for uprosertib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.