This phase I/II trial studies the side effects and the best dose of Akt inhibitor GSK2141795 when given together with dabrafenib and trametinib and to see how well they work in treating patients with stage IIIC-IV cancer. Akt inhibitor GSK2141795, dabrafenib, and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving Akt inhibitor GSK2141795 with dabrafenib and trametinib may be a better treatment for 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
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.
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 Dabrafenib Trametinib
For people ages 18 years and up
Patients must not have uncontrolled hypertension (defined as systolic blood pressure
140 mm Hg and/or diastolic blood pressure> 90 mm Hg which cannot be controlled by anti-hypertensive therapy)
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