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

NCT02368691 | Terminated Phase 2 Results DMC

• 1 other identifier: G200901
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 7

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).

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate, in Centrally Confirmed Androgen Receptor Positive (AR+) Subjects

  To estimate the clinical benefit rate (defined as complete response, partial response, or stable disease) according to Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST) as assessed by CT or MRI in subjects with centrally confirmed AR+ status. Clinical Benefit Rate=CR+PR+SD. Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease, \<30% decrease in sum of the longest diameter of target lesions.

  Sixteen (16) weeks

Secondary Outcomes (6)

• Clinical Benefit Rate, in Full Analysis Set

  Sixteen (16) weeks

• Best Overall Response

  From treatment initiation to end of treatment (up through 11 months of treatment, median duration of treatment 1.9 months).

• Progression Free Survival

  From treatment initiation to tumor progression or death. PFS was assessed up to 11 months of treatment; median duration of treatment, 1.9 months

• Time-to-progression

  From treatment initiation to tumor progression or death. Time to progression was assessed up to 11 months of treatment; median duration of treatment, 1.9 months

• Duration of Response

  From time of documented tumor response to tumor progression or death. Duration of response was assessed through 11 months; median treatment duration, 1.9 months

Other Outcomes (1)

• Number of Participants With Adverse Events

  Up to twelve (12) months

Study Arms (1)

GTx-024

EXPERIMENTAL

GTx-024 capsules, 18 mg PO once-daily for up to 12 months

Drug: GTx-024

Interventions

GTx-024 DRUG

GTx-024 softgel capsules will be administered once-daily to a total dose of 18 mg

Also known as: Enobosarm, Ostarine, S-22

GTx-024

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• GTx: lead

Study Sites (7)

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Lakeland Regional Health Care/Cancer Center

Lakeland, Florida, 33805, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

St. Vincent Frontier Cancer Center

Billings, Montana, 59102, United States

Location

The West Clinic, PC

Memphis, Tennessee, 38120, United States

Location

US Oncology / Texas Oncology, P.A.

Houston, Texas, 77024, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

ostarine

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Early termination due to lack of efficacy and limited data reported.

Results Point of Contact

• Title: Mary Breitmeyer
• Organization: Oncternal

MBreitmeyer@oncternal.com

858-434-1113

Study Officials

• Hope S Rugo, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: February 10, 2015
• First Posted: February 23, 2015
• Study Start: June 1, 2015
• Primary Completion: September 22, 2017
• Study Completion: September 22, 2017
• Last Updated: November 18, 2020
• Results First Posted: October 30, 2020

Record last verified: 2020-10

Locations

US (7)