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Efficacy and Safety of GTx-024 in Patients With Androgen Receptor-Positive Triple Negative Breast Cancer (AR+ TNBC)

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ClinicalTrials.gov Identifier: NCT02368691
Recruitment Status : Terminated (Lack of Efficacy)
First Posted : February 23, 2015
Last Update Posted : September 26, 2017
Sponsor:
Information provided by (Responsible Party):
GTx

Brief Summary:
The purpose of this study is to determine if GTx-024 is effective and safe in the treatment of patients with advanced, androgen receptor positive triple negative breast cancer (AR+ TNBC).

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Drug: GTx-024 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open Label, Multi-Center, Multinational Study Investigating The Efficacy and Safety Of GTx-024 On Advanced, Androgen Receptor-Positive Triple Negative Breast Cancer (AR+ TNBC)
Actual Study Start Date : June 2015
Actual Primary Completion Date : September 22, 2017
Actual Study Completion Date : September 22, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: GTx-024
GTx-024 capsules, 18 mg PO once-daily for up to 12 months
Drug: GTx-024
GTx-024 softgel capsules will be administered once-daily to a total dose of 18 mg
Other Names:
  • Enobosarm
  • Ostarine
  • S-22




Primary Outcome Measures :
  1. Clinical benefit rate, in centrally confirmed AR+ subjects [ Time Frame: Sixteen (16) weeks ]
    To estimate the clinical benefit rate (defined as complete response, partial response, or stable disease) according to RECIST 1.1 in subjects with centrally confirmed AR+ status


Secondary Outcome Measures :
  1. Clinical benefit rate, in full analysis set [ Time Frame: Sixteen (16) weeks ]
    To estimate the clinical benefit rate in all subjects who receive at least one dose of study medication (full analysis set), regardless of central confirmation of AR status.

  2. Clinical benefit rate [ Time Frame: Twenty-four (24) weeks ]
    To estimate the proportion of subjects who achieve clinical benefit

  3. Objective response rate [ Time Frame: Twenty-four (24) weeks ]
    To estimate the objective response rate (defined as complete response or partial response) according to RECIST 1.1.

  4. Best overall response [ Time Frame: From treatment initiation to end of treatment ]
    To assess best overall response as measured by RECIST 1.1 from the start of study treatment until the end of treatment taking into account any requirement for confirmation.

  5. Progression free survival [ Time Frame: From treatment initiation to tumor progression or death ]
    To assess progression free survival defined as the time elapsed between initiation of treatment and tumor progression as measured by RECIST 1.1 or death.

  6. Time-to-progression [ Time Frame: From treatment initiation to tumor progression or death ]
    To assess time to progression defined as time elapsed between treatment initiation and tumor progression as measured by RECIST 1.1 or death due to disease progression.

  7. Duration of response [ Time Frame: From time of documented tumor response to tumor progression or death ]
    To assess the duration of response defined as the time from documentation of tumor response to disease progression or death

  8. Objective response rate [ Time Frame: Sixteen (16) weeks ]
    To estimate the objective response rate (defined as complete response or partial response) according to RECIST 1.1.

  9. Overall survival [ Time Frame: Up to twenty-four (24) months ]
    To estimate overall survival defined as the time from treatment initiation until death or date of last follow up to a maximum of 24 months post treatment initiation.


Other Outcome Measures:
  1. Number of adverse events [ Time Frame: Up to twelve (12) months ]
    To describe the safety profile in subjects with TNBC and centrally confirmed AR+ as well as in all subjects enrolled and treated.

  2. Pharmacokinetic assessment [ Time Frame: Up to twelve (12) months ]
    To describe the plasma concentrations of GTx-024 and GTx-024 glucuronide at each of the assessed time points.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able and willing to give voluntary, written and signed, informed consent
  • Women ≥ 18 years of age
  • Women with TNBC who have received at least one but no more than two prior chemotherapy regimens for TNBC
  • Confirmation of AR+ (defined as ≥ 10% nuclear AR staining by immunohistochemistry [IHC]) TNBC in either the primary or metastatic lesion, assessed during the screening period by a local laboratory or by medical history
  • TNBC confirmed by medical history as: human epidermal growth factor receptor 2 [HER2]-negative (confirmed by IHC 0, 1+ regardless of fluorescence in situ hybridization [FISH] ratio; IHC 2+ with FISH ratio lower than 2.0 or HER2 gene copy less than 6.0; FISH ratio of 0, indicating gene deletion, when positive and negative in situ hybridization [ISH] controls are present); estrogen receptor (ER) negative (confirmed as ER expression less than or equal to 1% positive tumor nuclei); progesterone receptor negative (confirmed as progesterone receptor expression less than or equal to 1% positive tumor nuclei)
  • Availability of paraffin embedded or formalin fixed tumor tissue; OR, a minimum of 10 and up to 20 slides of archived tumor tissue for central laboratory confirmation of AR status and molecular subtyping. Metastatic tumor tissue is preferred when possible
  • Subjects must have either measurable disease or bone-only non-measurable disease, evaluable according to RECIST 1.1
  • Subjects with bone metastases should be treated with intravenous bisphosphonates or subcutaneous denosumab (or investigator preferred standard of care) prior to and during the trial, unless there is a contraindication or subject intolerance to these therapies
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the time of screening and enrollment
  • Negative pregnancy test in women of childbearing potential (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization), no more than 7 days before the first dose of study treatment
  • For women of childbearing potential who are sexually active, agreement to use a highly effective, non-hormonal form of contraception during and for at least 6 months after completion of study treatment; OR, a fertile male partner willing and able to use effective non-hormonal of contraception (barrier method of contraception in conjunction with spermicidal jelly, or surgical sterilization) during and for at least 6 months after completion of study treatment
  • Adequate organ function as shown by:

    • Absolute neutrophil count ≥ 1,000 cells/mm3
    • Platelet count ≥ 100,000 cells/mm3
    • Hemoglobin ≥ 9 g/dL
    • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 Upper Limit of the Normal range (ULN) (or ≤ 5 if hepatic metastases are present)
    • Total serum bilirubin ≤ 2.0 × ULN (unless the subject has documented Gilbert Syndrome)
    • Alkaline phosphatase levels ≤ 2.5 × ULN (≤ 5 × ULN in subjects with liver metastasis)
    • Serum creatinine < 2.0 mg/dL or 177 μmol/L
    • International normalized ratio (INR), activated partial thromboplastin time (aPTT), or partial thromboplastin time (PTT) < 1.5 × ULN (unless on anticoagulant treatment at screening)
  • Able to swallow capsules
  • Any toxicity from prior chemotherapy has resolved or Grade 1 (NCI-CTCAE, Version 4.0)

Exclusion Criteria:

  • Life expectancy < 4 months;
  • Subjects with radiographic evidence of central nervous system (CNS) metastases as assessed by computerized tomography (CT) or magnetic resonance imaging (MRI) that are not well controlled (symptomatic or requiring control with continuous corticosteroid therapy [e.g., dexamethasone]). Note: Subjects with CNS metastases are permitted to participate in the study if the CNS metastases are medically well controlled prior to screening (as assessed by the Investigator) after receiving local therapy (irradiation, surgery, etc.)
  • Radiotherapy within 14 days prior to first dose of study treatment
  • Have, in the judgment of the Investigator, a clinically significant concurrent illness or psychological, familial, sociological, geographical, or other concomitant condition that would not permit adequate follow-up and compliance with the study protocol
  • Positive hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection at screening
  • Positive human immunodeficiency virus (HIV) infection at screening
  • Prior treatment with any anti-androgens, including but not limited to, enzalutamide and bicalutamide
  • Major surgery within 28 days of the first dose of study treatment
  • Be currently taking or have previously taken testosterone, methyltestosterone, oxandrolone (Oxandrin®), oxymetholone, danazol, fluoxymesterone (Halotestin®), testosterone-like agents (such as dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or anti-androgens
  • Treatment with any of the following hormone replacement therapies, unless discontinued at least 14 days prior to the first dose of study treatment:

    • Estrogens
    • Megesterol acetate
  • Treatment with any investigational agent within 28 days before the first dose of study treatment
  • Another active cancer (excluding adequately treated basal cell carcinoma or cervical intraepithelial neoplasia [CIN]/cervical carcinoma in situ or melanoma in situ). Prior history of other cancer is allowed as long as there is no active disease within the prior 5 years
  • Subject has a concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases subject risk, in the opinion of the Investigator, such as but not limited to:

    • Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTcB (corrected according to Bazett's formula) interval > 470 msec; serious uncontrolled cardiac arrhythmia grade II or higher according to NYHA; uncontrolled hypertension (systolic > 150 and/or diastolic > 100 mm Hg)
    • Acute and chronic active infectious disorders and non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy
    • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
  • Current treatment with intravenous bisphosphonate or denosumab with elevated serum calcium corrected for albumin or ionized calcium levels outside institutional normal limits at screening
  • History of non-compliance to medical regimens
  • Subjects unwilling to or unable to comply with the protocol procedures as assessed by the Investigator
  • Concurrent participation in another therapeutic clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02368691


Locations
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United States, Florida
Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
Lakeland Regional Health Care/Cancer Center
Lakeland, Florida, United States, 33805
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Montana
St. Vincent Frontier Cancer Center
Billings, Montana, United States, 59102
United States, Tennessee
The West Clinic, PC
Memphis, Tennessee, United States, 38120
United States, Texas
US Oncology / Texas Oncology, P.A.
Houston, Texas, United States, 77024
Sponsors and Collaborators
GTx
Investigators
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Principal Investigator: Hope S Rugo, MD University of California, San Francisco

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Responsible Party: GTx
ClinicalTrials.gov Identifier: NCT02368691     History of Changes
Other Study ID Numbers: G200901
First Posted: February 23, 2015    Key Record Dates
Last Update Posted: September 26, 2017
Last Verified: September 2017
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs