Akt Inhibitor GSK2141795, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer
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|ClinicalTrials.gov Identifier: NCT01902173|
Recruitment Status : Suspended (Temporarily stopped for assessment. Contact firstname.lastname@example.org for specifics)
First Posted : July 18, 2013
Last Update Posted : July 2, 2017
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm Recurrent Colon Carcinoma Recurrent Melanoma Recurrent Ovarian Carcinoma Stage IIIC Colon Cancer Stage IIIC Ovarian Cancer Stage IIIC Skin Melanoma Stage IV Skin Melanoma||Drug: Akt Inhibitor GSK2141795 Drug: Dabrafenib Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Trametinib||Phase 1 Phase 2|
I. To assess the safety of dabrafenib in combination with Akt inhibitor GSK2141795 (GSK2141795) and select the optimal dose of GSK2141795 for the phase II portion in patients with BRAF mutant cancer. (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 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)
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).
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 Akt inhibitor GSK2141795 followed by a phase II study. Dose escalation of dabrafenib, trametinib, and Akt inhibitor GSK2141795 will be initiated after completion of the dabrafenib + GSK2141795 phase I dose escalation.
Dabrafenib and Akt inhibitor GSK2141795: Patients receive dabrafenib orally (PO) twice daily (BID) and Akt inhibitor GSK2141795 PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dabrafenib, trametinib, and Akt inhibitor GSK2141795: Patients receive dabrafenib PO BID, trametinib PO QD, and Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||97 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||July 19, 2013|
|Estimated Primary Completion Date :||June 30, 2017|
Experimental: Treatment (Akt inhibitor GSK2141795, dabrafenib, trametinib)
Dabrafenib and Akt inhibitor GSK2141795: Patients receive dabrafenib PO BID and Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dabrafenib, trametinib, and Akt inhibitor GSK2141795: Patients receive dabrafenib PO BID, trametinib PO QD, and Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Drug: Akt Inhibitor GSK2141795
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum-tolerated dose (MTD) of Akt inhibitor GSK2141795, determined according to incidence of dose-limiting toxicity, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) [ Time Frame: 2 months ]
- Objective response rate (confirmed and unconfirmed, complete and partial responses) as assessed by RECIST version 1.1 (Phase II) [ Time Frame: Up to 3 years ]
- Overall survival (Phase II) [ Time Frame: From date of registration to date of death due to any cause, assessed up to 3 years ]Estimated with 95% confidence interval.
- Progression-free survival as assessed by RECIST version 1.1 (Phase II) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years ]Estimated with 95% confidence interval.
- Toxicity rate graded by the NCI CTCAE version 4.0 (Phase II) [ Time Frame: Up to 3 years ]
- Pharmacokinetic parameters [ Time Frame: Baseline, pre-dose and 1, 2, 4, and 8 hours on day 15, and pre-dose day 29 ]
- Prevalence of markers [ Time Frame: Up to 3 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01902173
|United States, California|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|UCLA / Jonsson Comprehensive Cancer Center|
|Los Angeles, California, United States, 90095|
|California Pacific Medical Center-Pacific Campus|
|San Francisco, California, United States, 94115|
|UCSF Medical Center-Mount Zion|
|San Francisco, California, United States, 94115|
|United States, Colorado|
|University of Colorado Cancer Center - Anschutz Cancer Pavilion|
|Aurora, Colorado, United States, 80045|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|United States, Ohio|
|Cleveland Clinic Foundation|
|Cleveland, Ohio, United States, 44195|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Oregon|
|Clackamas Radiation Oncology Center|
|Clackamas, Oregon, United States, 97015|
|Providence Milwaukie Hospital|
|Milwaukie, Oregon, United States, 97222|
|Providence Newberg Medical Center|
|Newberg, Oregon, United States, 97132|
|Providence Willamette Falls Medical Center|
|Oregon City, Oregon, United States, 97045|
|Providence Portland Medical Center|
|Portland, Oregon, United States, 97213|
|Providence Saint Vincent Medical Center|
|Portland, Oregon, United States, 97225|
|Oregon Health and Science University|
|Portland, Oregon, United States, 97239|
|United States, Washington|
|PeaceHealth Southwest Medical Center|
|Vancouver, Washington, United States, 98664|
|Principal Investigator:||Antoni Ribas||Southwest Oncology Group|