Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Metastatic Triple-Negative Breast Cancer

NCT01964924 | Completed Phase 2 Results

• 9 other identifiers: NCI-2013-018952013C0069OSU 131179455N01CM00070N01CM00100P30CA016058UM1CA186712UM1CA186716
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 8

Brief Summary

This phase II trial studies how well trametinib and v-akt murine thymoma viral oncogene homolog 1 (Akt) inhibitor GSK2141795 work in treating patients with triple-negative breast cancer (breast cancer cells that do not have estrogen receptors, progesterone receptors, or large amounts of human epidermal growth factor receptor 2 \[HER2/neu\] protein) that has spread to other places in the body. Trametinib and Akt inhibitor GSK2141795 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR), Defined as the Proportion of Patients Who Have Had a Partial Response (PR) or Complete Response (CR) (RECIST 1.1 Based) Within the First 6 Months After Initiation of Therapy With Trametinib

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  6 months

Secondary Outcomes (9)

• Clinical Benefit Rate (CBR = CR+PR+Stable Disease [SD])

  Up to 52 weeks

• Duration of Objective Response

  up to 52 weeks

• Incidence of Adverse Events That Are Classified as Either Possibly, Probably, or Definitely Related to Study Treatment

  Up to 52 weeks

• Incidence of Severe (Grade 3+) Adverse Events or Toxicities Graded Per NCI CTCAE Version 4.0

  Up to 52 weeks

• Overall Survival

  Start date of the treatment to the date of the event (i.e., death) or the date of last follow-up to evaluate that event, assessed up to 52 weeks

Other Outcomes (2)

• Predictive Value of PTEN and Other Biomarkers on Patient Outcome (Survival, ORR, and CBR)

  At time of disease progression, assessed up to 52 weeks

• Protein Intensity Fold-change Ratios Assessed by Reverse Phase Protein Assay Intensity Values

  Up to 52 weeks

Study Arms (1)

Treatment (trametinib, Akt inhibitor GSK2141795)

EXPERIMENTAL

PART 1: Patients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression continue to Part 2. PART 2: Patients receive trametinib as in Part 1 and also receive 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; Drug: Trametinib

Interventions

Akt Inhibitor GSK2141795 DRUG

Given PO

Also known as: GSK2141795, Oral Akt Inhibitor GSK2141795

Treatment (trametinib, Akt inhibitor GSK2141795)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (trametinib, Akt inhibitor GSK2141795)

Trametinib DRUG

Given PO

Also known as: GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist

Treatment (trametinib, Akt inhibitor GSK2141795)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed metastatic invasive breast cancer that is negative for the estrogen receptor (ER), progesterone receptor (PR) and HER2 by institutional guidelines
• Patients must have measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\])
• Patients must have had exposure to at least 1 and no more than 3 prior chemotherapy regimens for the treatment of metastatic breast cancer
• Patients must consent to both a pretreatment and a post-treatment mandatory research biopsy prior to enrolling on trial, and therefore, must have tissue (excluding bone or brain) that is amenable to biopsy
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy of greater than 3 months
• Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events version 4 (CTCAE v4) grade =\< 1 (except alopecia) at the time of enrollment
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 75,000/mcL
• Total bilirubin =\< 1.5 × institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 × institutional upper limit of normal
• Left ventricular ejection fraction (LVEF) \>= institutional lower limit of normal by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
• Serum creatinine =\< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) \>= 50 mL/min OR 24-hour urine creatinine clearance \>= 50 mL/min
• Patients must have controlled blood pressure with a systolic blood pressure \< 140 mmHg and diastolic \< 90 mmHg; anti-hypertensive medications are permitted

You may not qualify if:

• History of another malignancy
• Exception: patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible
• History of interstitial lung disease or pneumonitis
• History of type I diabetes mellitus; if a patient has type II diabetes, they must have a hemoglobin (hemoglobin A1C) =\< 8%; patients with a screening fasting glucose \> 120 mg/dL will be excluded
• Uncontrolled hypothyroidism; patients must have a normal thyroid-stimulating hormone (TSH) per institutional standards at baseline
• Patients who are receiving any other investigational agents
• Individuals with symptomatic or progressive brain metastases are ineligible; subjects with treated brain metastases are eligible if they have no radiographic or other signs of progression in the brain for \>= 3 weeks after completion of local therapy; any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for \>= 3 weeks prior to study enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to trametinib monotherapy or trametinib in combination with GSK2141795
• Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:
• Other anti-cancer therapy while on study treatment (megestrol if used as an appetite stimulant is allowed)
• The concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra \[ma huang\], gingko biloba, yohimbe, saw palmetto, or ginseng)
• Patients receiving strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible
• History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, history of hyperviscosity or hypercoagulability syndromes; visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure \> 21 mm Hg
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study, breastfeeding should be discontinued if the mother is treated with trametinib monotherapy or trametinib in combination with GSK2141795

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• GlaxoSmithKline: collaborator

Study Sites (8)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

GSK2141795; trametinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Bhuvaneswari Ramaswamy
• Organization: The Ohio State University Comprehensive Cancer Center

Bhuvaneswari.Ramaswamy@osumc.edu

614-293-8858

Study Officials

• Bhuvaneswari Ramaswamy, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2013
• First Posted: October 17, 2013
• Study Start: October 2, 2013
• Primary Completion: January 20, 2017
• Study Completion: April 23, 2018
• Last Updated: September 20, 2019
• Results First Posted: September 20, 2019

Record last verified: 2019-08

Locations

US (8)