ER+ and AR+ Breast CancerPhase 2NCT02463032
Efficacy and Safety of GTx-024 in Patients With Estrogen Receptor (ER)+/Androgen Receptor (AR)+ Breast Cancer
A Phase 2 study testing GTx-024 in people with ER+ and AR+ Breast Cancer, run by GTx at 4 sites in United States.
Trial summary
The purpose of this study is to determine if GTx-024 at different dosages (9 mg or 18 mg) is effective and safe in the treatment of patients with metastatic or locally advanced Estrogen Receptor (ER)+ and Androgen Receptor (AR)+ breast cancer in postmenopausal women. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- ER+ and AR+ Breast Cancer
- What is being tested?
- GTx-024
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 4 sitesUnited States
- Study dates
- Aug 2015to Mar 2019
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult women (≥ 18 years of age) with metastatic or recurrent locally advanced BC, not amenable to curative treatment by surgery or radiotherapy, with objective evidence of disease progression.
- Women must have received ≥ 1 prior hormonal treatment(s) in the metastatic or adjuvant setting. If the most recent hormonal treatment was in the metastatic setting, duration of response (tumor regression or stabilization of disease) to this specific course of therapy must be ≥ 6 months. If the most recent hormonal treatment was in the adjuvant setting, duration of response (disease free) to this specific course of therapy must be ≥ 3 years
- Histological or cytological confirmation of ER+ BC as assessed by a local laboratory using slides, paraffin blocks, or paraffin sample or by medical history: ER+ (confirmed as ER expression more than or equal to 1% positive tumor nuclei)
- Human epidermal growth factor receptor 2 (HER2)-negative tumor by local laboratory testing (immunohistochemistry [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)
- Availability of paraffin embedded or formalin fixed tumor tissue; OR, a minimum of 10 and up to 20 slides of archived tumor tissue or new biopsy, if archived tissue is unavailable for central laboratory confirmation of AR status and molecular subtyping. Metastatic tumor tissue is preferred when possible.
- Postmenopausal women. Postmenopausal status is defined by the National Comprehensive Cancer Network as either:
Show all 24Show fewer
- Age ≥ 55 years and one year or more of amenorrhea
- Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/mL
- Age < 55 years and surgical menopause with bilateral oophorectomy a. Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression at the time of screening. Long term use (>6 months prior to screening) is permitted
- Radiological or clinical evidence (bone scan, computerized tomography [CT], and magnetic resonance Imaging [MRI]) of recurrence or progression within 30 days before randomization
- Subject must have either measurable disease or bone only non measurable disease, according to RECIST1.1
- Adequate organ function as shown by:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
- Platelet count ≥ 100,000 cells/mm3
- Hemoglobin (Hgb) ≥ 9.0 g/dL
- Serum aspartate aminotransferase (AST) and alanine transaminase (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 (aPTT), or partial thromboplastin time (PTT) < 1.5 × ULN (unless on anticoagulant treatment at screening)
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Subjects with bone metastases should be treated with intravenous bisphosphonates or subcutaneous denosumab (or investigator preferred standard of care) prior to and/or during the trial, unless there is a contraindication or subject intolerance to these therapies. For patients who are normocalcemic, therapy can be initiated at the time the patient initiates study drug
- Subject is able to swallow capsules
- Able and willing to give voluntary, written and signed informed consent before any screening procedure and according to local guidelines
Who cannot join
- Previously received > 1 course of chemotherapy (not including immunotherapies or targeted therapies) for the treatment of metastatic
- Note: Subjects may have received 1 course of chemotherapy prior to surgery for the treatment of locally advanced disease and 1 course of chemotherapy for the treatment of metastatic BC; however, if surgery could not be performed, this will count as the 1 chemotherapy course allowed prior to study
- Known hypersensitivity to any of the GTx-024 components or subjects previously received treatment with SARM
- Subjects with radiographic evidence of central nervous system (CNS) metastases as assessed by CT or 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 and stable for at least 28 days after receiving local therapy (irradiation, surgery, etc.)
- Radiotherapy within 14 days prior to randomization except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to randomization. Subjects must have recovered from radiotherapy toxicities prior to randomization
Show all 22Show fewer
- Currently receiving hormone replacement therapy, unless discontinued prior to screening
- Subjects positive for Human Immunodeficiency Virus (HIV)
- 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)
- 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
- Major surgery within 28 days before randomization
- Positive hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection at screening
- History of non-compliance to medical regimens
- Subjects unwilling to or unable to comply with the protocol
- Subject is currently receiving treatment with any agent listed on the prohibited medication list
- Treatment with any investigational product within < 4 half-lives for each individual investigational product OR 28 days prior to randomization
- Current treatment with intravenous bisphosphonate or denosumab with elevated serum calcium corrected for albumin or ionized calcium levels outside institutional normal limits at screening
Trial locations and contacts
4 sites in 1 country.
United States4 sites
St. Vincent Frontier Cancer Center
Billings, Montana, 59102
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Holy Cross Hospital
Fort Lauderdale, Florida, 33308
The West Clinic, PC
Memphis, Tennessee, 38120
About this study
Official title: A Phase 2 Open Label, Multi-Center, Multinational, Randomized, Parallel Design Study Investigating The Efficacy and Safety Of GTx-024 On Metastatic or Locally Advanced ER+/AR+ Breast Cancer (BC) in Postmenopausal Women
The purpose of this study is to determine if GTx-024 at different dosages (9 mg or 18 mg) is effective and safe in the treatment of patients with metastatic or locally advanced Estrogen Receptor (ER)+ and Androgen Receptor (AR)+ breast cancer in postmenopausal women.
- Conditions
- ER+ and AR+ Breast Cancer
- Being tested
- GTx-024
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GTx-024Drug
To determine whether either or both doses result in an acceptable clinical benefit rate.
| Study group | Role | What they receive |
|---|---|---|
| GTx-024 9 mg | Experimental | Drug: GTx-024 GTx-024 softgel capsules will be administered once daily to a total dose of 9 mg Receives: Drug: GTx-024 |
| GTx-024 18 mg | Experimental | Drug: GTx-024 GTx-024 softgel capsules will be administered once daily to a total dose of 18 mg Receives: Drug: GTx-024 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Rate, in Centrally Confirmed Androgen Receptor (AR)+ Subjects
To estimate the clinical benefit rate (defined as complete response, partial response, or stable disease) according to RECIST 1.1, in subjects with estrogen receptor positive/androgen receptor positive (ER+/AR+) BC who have centrally confirmed AR+ status. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or 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; Clinical Benefit Rate (CBR)= CR + PR + SD.
Measured: 24 weeks
Secondary outcomes (5)
Clinical Benefit Rate, in Full Analysis Set
To estimate the clinical benefit response rate in all subjects randomized who receive at least one dose of study medication (the FAS) regardless of AR status as determined by the central laboratory. o estimate the clinical benefit rate (defined as complete response, partial response, or stable disease) according to RECIST 1.1, in subjects with estrogen receptor positive/androgen receptor positive (ER+/AR+) BC who have centrally confirmed AR+ status. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or 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; Clinical Benefit Rate (CBR)= CR + PR + SD.
Measured: 24 weeks
Objective Response (CR + PR) in AR+ Patients
To estimate the clinical benefit rate (defined as complete response, partial response, or stable disease) according to RECIST 1.1, in subjects with estrogen receptor positive/androgen receptor positive (ER+/AR+) BC who have centrally confirmed AR+ status. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or 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; Clinical Benefit Rate (CBR)= CR + PR + SD.
Measured: 24 weeks
Best Overall Response in AR+ Patients
To estimate the best overall response of GTx-024 9 mg and 18 mg
Measured: From treatment initiation to end of treatment
Progression Free Survival in All Subjects
To estimate the progression free survival of subjects receiving Gtx-024 9 mg and 18 mg. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Subjects were assessed up through 24 months.
Measured: From randomization to tumor progression or death
Time to Progression in All Subjects
To estimate the time to progression in subjects receiving Gtx-024 9 mg and 18 mg in all subjects. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Time to progression was assessed up through 24 months.
Measured: From randomization to tumor progression or death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2015 (estimated)
- Study startAug 2015
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ER+ and AR+ Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 136 participants (actual)
Sponsor and investigators
- Lead sponsor
- GTx
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Beth A Overmoyer, MD, Principal investigator, Susan Smith Center for Women's Cancers, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02463032
- Sponsor's protocol ID
- G200802
- Status last verified
- Dec 2020
- First submitted
- 2 Jun 2015
- Last updated
- 9 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Palmieri C, Linden H, Birrell SN, Wheelwright S, Lim E, Schwartzberg LS, Dwyer AR, Hickey TE, Rugo HS, Cobb P, O'Shaughnessy JA, Johnston S, Brufsky A, Tilley WD, Overmoyer B. Activity and safety of enobosarm, a novel, oral, selective androgen receptor modulator, in androgen receptor-positive, oestrogen receptor-positive, and HER2-negative advanced breast cancer (Study G200802): a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial. Lancet Oncol. 2024 Mar;25(3):317-325. doi: 10.1016/S1470-2045(24)00004-4. Epub 2024 Feb 8.
PubMed 38342115
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open Label, Multi-Center, Multinational, Randomized, Parallel Design Study Investigating The Efficacy and Safety Of GTx-024 On Metastatic or Locally Advanced ER+/AR+ Breast Cancer (BC) in Postmenopausal Women
- ClinicalTrials.gov ID
- NCT02463032
- Acronym / sponsor ID
- G200802
- Conditions
- ER+ and AR+ Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 136 participants (actual)
- Lead sponsor
- GTxIndustry (pharma, biotech, devices)
- Study start
- Aug 2015 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 4 Jun 2015 (estimated)
- Results
- Posted 9 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if GTx-024 at different dosages (9 mg or 18 mg) is effective and safe in the treatment of patients with metastatic or locally advanced Estrogen Receptor (ER)+ and Androgen Receptor (AR)+ breast cancer in postmenopausal women.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GTx-024 9 mg | Experimental | Drug: GTx-024Drug: GTx-024 GTx-024 softgel capsules will be administered once daily to a total dose of 9 mg |
| GTx-024 18 mg | Experimental | Drug: GTx-024Drug: GTx-024 GTx-024 softgel capsules will be administered once daily to a total dose of 18 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Adult women (≥ 18 years of age) with metastatic or recurrent locally advanced BC, not amenable to curative treatment by surgery or radiotherapy, with objective evidence of disease progression.
- Histological or cytological confirmation of ER+ BC as assessed by a local laboratory using slides, paraffin blocks, or paraffin sample or by medical history: ER+ (confirmed as ER expression more than or equal to 1% positive tumor nuclei)
- Human epidermal growth factor receptor 2 (HER2)-negative tumor by local laboratory testing (immunohistochemistry [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)
- Availability of paraffin embedded or formalin fixed tumor tissue; OR, a minimum of 10 and up to 20 slides of archived tumor tissue or new biopsy, if archived tissue is unavailable for central laboratory confirmation of AR status and molecular subtyping. Metastatic tumor tissue is preferred when possible.
- Postmenopausal women. Postmenopausal status is defined by the National Comprehensive Cancer Network as either:
Key exclusion criteria (22 listed)
- Previously received > 1 course of chemotherapy (not including immunotherapies or targeted therapies) for the treatment of metastatic
- Known hypersensitivity to any of the GTx-024 components or subjects previously received treatment with SARM
- Subjects with radiographic evidence of central nervous system (CNS) metastases as assessed by CT or MRI that are not well controlled (symptomatic or requiring control with continuous corticosteroid therapy [e.g., dexamethasone])
- Radiotherapy within 14 days prior to randomization except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to randomization. Subjects must have recovered from radiotherapy toxicities prior to randomization
- Currently receiving hormone replacement therapy, unless discontinued prior to screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GTx-024To determine whether either or both doses result in an acceptable clinical benefit rate. | Drug | GTx-024 18 mg, GTx-024 9 mg |
Primary outcome
Clinical Benefit Rate, in Centrally Confirmed Androgen Receptor (AR)+ Subjects
Time frame: 24 weeks
To estimate the clinical benefit rate (defined as complete response, partial response, or stable disease) according to RECIST 1.1, in subjects with estrogen receptor positive/androgen receptor positive (ER+/AR+) BC who have centrally confirmed AR+ status. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or 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; Clinical Benefit Rate (CBR)= CR + PR + SD.
5 secondary outcomes
Clinical Benefit Rate, in Full Analysis Set
Time frame: 24 weeks
Objective Response (CR + PR) in AR+ Patients
Time frame: 24 weeks
Best Overall Response in AR+ Patients
Time frame: From treatment initiation to end of treatment
Progression Free Survival in All Subjects
Time frame: From randomization to tumor progression or death
Time to Progression in All Subjects
Time frame: From randomization to tumor progression or death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38342115Palmieri C, Linden H, Birrell SN, Wheelwright S, Lim E, Schwartzberg LS, Dwyer AR, Hickey TE, Rugo HS, Cobb P, O'Shaughnessy JA, Johnston S, Brufsky A, Tilley WD, Overmoyer B. Activity and safety of enobosarm, a novel, oral, selective androgen receptor modulator, in androgen receptor-positive, oestrogen receptor-positive, and HER2-negative advanced breast cancer (Study G200802): a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial. Lancet Oncol. 2024 Mar;25(3):317-325. doi: 10.1016/S1470-2045(24)00004-4. Epub 2024 Feb 8.
Related trials for ER+ and AR+ Breast Cancer
Active, not recruitingPhase 1
PAveMenT: Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer
Triple Negative Breast Cancer, Locally Advanced Breast Cancer
RecruitingPhase 1/2
Phase 1/2 Study to Evaluate EP0062 as Monotherapy and in Combination in Patients With Advanced or Metastatic AR+/HER-2-/ER+ Breast Cancer
Hormone Receptor-positive Breast Cancer, Hormone Receptor Positive HER-2 Negative Breast Cancer
RecruitingPhase 2
A Study of Enzalutamide, Enzalutamide in Combination With Mifepristone, or Chemotherapy in People With Metastatic Breast Cancer
Metastatic Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beth A Overmoyer, MD principal investigator
Susan Smith Center for Women's Cancers, Dana-Farber Cancer Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GTx-024 in people with ER+ and AR+ Breast Cancer, run by GTx at 4 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 24 inclusion and 22 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 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 9 Dec 2020). 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?
Clinical Benefit Rate, in Centrally Confirmed Androgen Receptor (AR)+ Subjects (time frame: 24 weeks). 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 NCT02463032, which also lists 1 linked publication.
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 9 Dec 2020.