Phase 2
Completed N=3
Uprosertib, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer
Hematopoietic and Lymphoid Cell Neoplasm · Locally Advanced Malignant Solid Neoplasm · Locally Advanced Melanoma · Metastatic Malignant Solid Neoplasm
Source: ClinicalTrials.gov NCT01902173 ↗
Enrolled (actual)
3
Serious AEs
59.1%
Results posted
Oct 2020
Primary outcomePrimary: Maximum-tolerated Dose (MTD) of Akt Inhibitor GSK2141795 in Combination With Dabrafenib. — 75 mg
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum-tolerated Dose (MTD) of Akt Inhibitor GSK2141795 in Combination With Dabrafenib. |
75 | — |
| PRIMARY Maximum-tolerated Dose (MTD) of Akt Inhibitor GSK2141795 in Combination With Dabrafenib and Trametinib. |
75 | — |
| PRIMARY 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) |
— | — |
| PRIMARY 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) |
— | — |
| SECONDARY Overall Survival (Phase II) of Patients Treated at the Phase I Determined MTD of Doublet Regimen |
— | — |
| SECONDARY Overall Survival (Phase II) of Patients Treated at the Phase I Determined MTD of Triplet Regimen |
— | — |
| SECONDARY Progression-free Survival as Assessed by RECIST Version 1.1 of the Doublet Regimen at the Phase I Determined MTD (Phase II) |
— | — |
| SECONDARY Progression-free Survival as Assessed by RECIST Version 1.1 of the Triplet Regimen at the Phase I Determined MTD (Phase II) |
— | — |
| SECONDARY Toxicity Rate of MTD Graded by the NCI CTCAE Version 4.0 (Phase II) |
— | — |
Eligibility Criteria
Inclusion Criteria
- PHASE I PORTION ELIGIBILITY CRITERIA:
- Patients must have BRAF^V600 mutant metastatic cancer irrespective of the histology or prior therapy; BRAF^V600 mutant status must be documented by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; use of an Food and Drug Administration (FDA)-approved test is preferred although other BRAF tests at a CLIA-certified laboratory may also be accepted
- Patients must have locally advanced unresectable stage IIIC or metastatic stage IV cancer with either progression to prior therapy or a newly diagnosed cancer that does not have an available treatment with curative intent
- Patients must have a complete physical examination and medical history within 28 days prior to registration
- Patients must have measurable or non-measurable disease; all measurable lesions must be assessed (by physical examination, computed tomography [CT], or magnetic resonance imaging [MRI] scan) within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration; all disease must be assessed and documented on the baseline tumor assessment form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
- All patients must undergo a CT or MRI of the brain within 42 days prior to registration; patients with asymptomatic brain metastases or previously treated brain metastases that are stable (i.e. not requiring corticosteroids) at the time of registration will be eligible
- Patients may have received prior systemic therapy (chemotherapy, immunotherapy, biologic therapy, or combination regimens); all adverse events associated with prior treatment must have resolved to = 1,200/ul (obtained within 28 days prior to registration)
- Platelets >= 100, 000/ul (obtained within 28 days prior to registration)
- Hemoglobin >= 9 g/dL (obtained within 28 days prior to registration)
- Total bilirubin = = 2.5 g/dL (obtained within 28 days prior to registration)
- Serum creatinine = = 50 mL/min (obtained within 28 days prior to registration)
- Patient must have a left ventricular ejection fraction >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition (MUGA) within 28 days prior to registration
- Patients with melanoma must have a serum lactate dehydrogenase (LDH) test performed within 28 days prior to registration
- Patients with human immunodeficiency virus (HIV) are eligible if they are not on antiviral agents and have adequate cluster of differentiation (CD)4 counts (>= 500 mm^3)
- Patients receiving anticoagulation treatment are allowed to participate with international normalized ratio (INR) established within the therapeutic range
- Women of childbearing potential must have a negative pregnancy test within 14 days of registration
- Patients must be able to retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels; patients who have feeding tubes can enroll in the study provided that the capsules do not need to be modified
- Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
- Patients must be >= 18 years of age
- Patients must have a serum albumin >= 2.5 g/dL within 28 days prior to registration
- PHASE II PORTION ELIGIBILITY CRITERIA:
- Patients must have histologically confirmed melanoma with BRAF^V600 mutation; patients must have stage IIIC or stage IV disease
- Patients must have received prior BRAF inhibitor
Data sourced from ClinicalTrials.gov (NCT01902173). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.