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Estrogen Receptor NegativePhase 2NCT01964924

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

A Phase 2 study testing Akt Inhibitor GSK2141795, Laboratory Biomarker Analysis and Trametinib in people with Estrogen Receptor Negative and HER2/Neu Negative, run by National Cancer Institute (NCI) at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Akt Inhibitor GSK2141795, Laboratory Biomarker Analysis and Trametinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
8 sitesUnited States
Study dates
2 Oct 2013to 23 Apr 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Patients must be at least 4 weeks from last radiation dose; patients must be at least 4 weeks from last chemotherapy, targeted therapy, or biologic therapy (exception allowed for a 2 week washout for patients who were on chemotherapy at less than a standard of care dose, as long as all other eligibility criteria are met); patients must be at least 4 weeks from last surgical procedure and recovered from all post-operative complications
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of trametinib monotherapy or in combination with GSK2141795 administration
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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
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  • 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
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Single Arm, Phase II Study of Single Agent Trametinib Followed by Trametinib in Combination With GSK2141795 in Patients With Advanced Triple Negative Breast Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the anti-tumor activity associated with trametinib monotherapy in patients with triple negative breast cancer (TNBC).

SECONDARY OBJECTIVES:

  1. To assess the anti-tumor activity associated with trametinib in combination with AKT inhibitor GSK2141795 after progression on trametinib in patients with metastatic TNBC.

II. To determine the progression-free survival following the initiation of treatment with trametinib monotherapy in patients with metastatic TNBC.

III. To determine the progression-free survival following the initiation of treatment with trametinib in combination with GSK2141795 in patients with metastatic TNBC.

IV. To determine the overall survival following the initiation of treatment with trametinib with GSK214179 in patients with metastatic TNBC.

  1. To determine the nature and degree of toxicities associated with trametinib monotherapy and trametinib in combination with GSK2141795 in patients with metastatic TNBC.

VI. To determine the biomarker potential of phosphatase and tensin homolog (PTEN) to predict response to single agent trametinib.

VII. To determine molecular markers of sensitivity and resistance to trametinib monotherapy and trametinib in combination with GSK2141795 in patients with metastatic TNBC.

OUTLINE:

PART 1: Patients receive trametinib orally (PO) once daily (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.

After completion of study treatment, patients are followed up every 3 months for 52 weeks.

Being tested
Akt Inhibitor GSK2141795, Laboratory Biomarker Analysis, Trametinib
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Akt Inhibitor GSK2141795Drug

    Also called GSK2141795, Oral Akt Inhibitor GSK2141795

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • TrametinibDrug

    Also called GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist

    Given PO

Study groups in NCT01964924
Study groupRoleWhat they receive
Treatment (trametinib, Akt inhibitor GSK2141795)ExperimentalPART 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.
Receives: Drug: Akt Inhibitor GSK2141795; Other: Laboratory Biomarker Analysis; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months

Secondary outcomes (9)

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

    The clinical benefit rate (CR+PR+SD) will be reported for patients after Part 1 and after Part 2.

    Measured: Up to 52 weeks

  2. Duration of Objective Response

    Summary statistics of duration of response for patients with objective response

    Measured: up to 52 weeks

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

    Incidence of adverse events for patients that are classified as either possibly, probably, or definitely related to study treatment graded by National Cancer Institute (NCI) CTCAE v4.0

    Measured: Up to 52 weeks

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

    NCI CommonTerminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for grading incidence of toxicities (grade 3+).

    Measured: Up to 52 weeks

  5. Overall Survival

    The Kaplan-Meier method will be used to estimate overall survival distribution.

    Measured: 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

  6. Progression-free Survival

    The Kaplan-Meier method will be used to estimate progression-free survival distribution.

    Measured: The duration of time from start of treatment to time of progression or death, whichever comes first, assessed up to 52 weeks

  7. Proportion of Patients Who go Off Treatment Due to Adverse Reactions

    The proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial was captured. These tolerability measures were assessed within each of the treatment parts independently. All patients who have received at least one dose of any of the therapeutic agents was evaluable for toxicity and tolerability.

    Measured: Up to 52 weeks

  8. Proportion of Patients Who Refuse Further Treatment for Lesser Toxicities That Inhibit Their Willingness to Continue Participation on the Trial

    Measured: Up to 52 weeks

  9. Tolerability of the Regimen Defined as the Number of Patients Who Required Dose Modifications and/or Dose Delays

    Measured: Up to 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2013 (estimated)
  2. Study start2 Oct 2013
  3. Primary completion20 Jan 2017
  4. Study completion23 Apr 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01964924
Sponsor's protocol ID
NCI-2013-01895
Other IDs
NCI-2013-01895, 2013C0069, OSU 13117, 9455, 9455, N01CM00070, N01CM00100, P30CA016058
Status last verified
Aug 2019
First submitted
15 Oct 2013
Last updated
20 Sep 2019
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Akt Inhibitor GSK2141795, Laboratory Biomarker Analysis and Trametinib in people with Estrogen Receptor Negative and HER2/Neu Negative, run by National Cancer Institute (NCI) at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01964924.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2019.

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