SWOG clinical trial number

"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."

Abbreviated Title
BRAF Mutant Metastatic Cancer
Status Notes
The study referenced above was temporarily closed to accrual on 10/31/2016.
Due to drug supply on this study, the study will be switched from temporarily closed to permanently closed with the same status date of 10/31/2016.
Limited: Institutions Listed on the Title Page

Research committees

Gastrointestinal Cancer


Dabrafenib GSK2141795 Trametinib Dimethyl Sulfoxide

Eligibility Criteria Expand/Collapse

Pt must have BRAF V600 mutant metastatic Ca irrespective of histology or prior therapy. BRAF mutant status must be documented by CLIA certified lab although use of an FDA-approved test is preferred. Pts progressing on prior BRAF inhibitor-based therapy & pts naive to BRAF inhibitor therapy are eligible. There will not be a break between progression on prior BRAF inhibitor therapy and start of protocol treatment. Prior systemic therapy (chemo, immuno, bio or combo), surgery and/or RT is allowed. Patients must have locally adv unresectable Stage IIIC or met Stage IV w/either progression to prior tx or newly diagnosed w/out available tx w/curative intent; have a complete physical exam and medical history w/in 28 days prior to reg; have measurable or non-measurable disease w/measurable lesions assessed w/in 28 days & tests to assess non-measurable disease performed w/in 42 days prior to reg; undergo CT or MRI of the brain w/in 42 days prior to reg; be willing to submit blood for PK; have available & be willing to submit baseline tissue taken at time of disease prog to prior BRAF inhibitor-based tx or have a site of disease that can be biopsied; have Zubrod PS of </= 1; have ANC >/= 1500, platelets >/= 100,000, hemoglobin >/= 9 g/dL, bili </= 1.5 x IULN, (or </= 2.5 x ULN for Gilbert's syndrome); AST & ALT </= 2.5 x IULN, creatinine </= 1.5 mg/dL or measured or calculated CrCl >/= 50 mL/min, LVEF >/= ILLN by ECHO or MUGA, and if melanoma LDH performed w/in 28 days prior to reg; if female, have negative pregnancy test w/in 14 days prior to reg; and be able to swallow capsules. HIV okay if pt not on antiviral agents and have adequate CD4 counts (>/= 500 mm3).

Patients must not have QTc >/= 480 msecs w/in 28 days prior to reg; have history of cardiac conditions per Sect 5.1r; be rec'g strong inhibitors or inducers of CYP3A or CYP2C8 or be planning to use herbal remedies or strong inhibitors or inducers of Pgp or Bcrp1 (see App 18.4); be pregnant or nursing; have uncontrolled intercurrent illness per 5.1y; have active Hep B or C virus infection; have history of allergic reaction per 5.1aa. Patients req'g therapeutic anticoagulation must have approval from physician per 5.1u.

Publication Information Expand/Collapse


A phase 1 study of triple targeted therapy with BRAF, MEK and AKT inhibitors for patients with BRAF mutated cancers

AP Algazi;J Moon;C Lao;B Chmielowski;K Kendra;K Lewis;R Gonzalez;K Kim;JE Godwin;B Curti;M Latkovic-Taber;S Lomeli;B Gufford;P Scumpia;R Lo;M Othus;A Ribas Cancer Jan 23. doi: 10.1002/cncr.35200. Online ahead of print

PMid: PMID38261444


SWOG S1221: A phase 1 dose escalation study co-targeting MAPK-dependent and MAPK-independent BRAF inhibitor resistance in BRAF mutant advanced solid tumors with dabrafenib, trametinib, and GSK2141795 (ClinicalTrials.gov NCT01902173)

A Algazi;J Moon;B Chmielowski;RS Lo;K Kendra;C Lao;K Lewis;R Gonzalez;KB Kim;JE Godwin;BD Curti;M Othus;A Ribas J Clin Oncol 35, 2017 (suppl; abstr 2578); American Society of Clinical Oncology Annual Meeting (June 2-6, 2017, Chicago, IL), poster session

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