Androgen Receptor PositivePhase 2NCT02971761
Pembrolizumab and Enobosarm in Treating Patients With Androgen Receptor Positive Metastatic Triple Negative Breast Cancer
A Phase 2 study testing Enobosarm, Laboratory Biomarker Analysis and Pembrolizumab in people with Androgen Receptor Positive and Estrogen Receptor Negative, run by City of Hope Medical Center at 7 sites in United States.
Trial summary
This phase II trial studies the side effects and how well pembrolizumab and enobosarm work in treating patients with androgen receptor positive triple negative breast cancer that has spread to other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Androgen Receptor Positive, Estrogen Receptor Negative, HER2/Neu Negative
- What is being tested?
- Enobosarm, Laboratory Biomarker Analysis and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 7 sitesUnited States
- Study dates
- 1 Jun 2017to 16 Aug 2022
- Phase
- Phase 2
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
- Documented informed consent
- Willing to provide a sample from a recently obtained (within 42 days prior to initiation of day 1) biopsy of a tumor lesion
- If recently-obtained samples are unavailable an archived metastatic specimen not previously irradiated may be submitted upon agreement from the study principal investigator (PI)
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
- Life expectancy of > 3 months
- Metastatic triple negative breast cancer (TNBC)
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- Measurable disease per RECIST version (v)1.1 criteria: at least 1 lesion of > 10 mm in long axis diameter for non-lymph nodes or > 15 mm in short axis diameter for lymph nodes that is serially measurable according to RECIST 1.1 using computerized tomography, magnetic resonance imaging, or panoramic and close-up color photography
- Histologically proven diagnosis of TNBC per current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline
- Estrogen receptor (ER) negative (ER expression =< 10% positive tumor nuclei), progesterone receptor (PR) negative (PR expression =< 10% positive tumor nuclei) and HER2 negative breast cancer by IHC and /or fluorescence in situ hybridization (FISH)
- Androgen receptor positive (AR+)
- Defined as >= 50% nuclear AR staining by immunohistochemistry (IHC) in either the primary or metastatic lesion
- NOTE: research testing of AR status is available at City of Hope (COH) Pathology
- Resolution of grade 2 and above toxicities of most recent therapy except for stable sensory neuropathy (=< grade 2) and alopecia
- Female (childbearing potential): use an adequate method of birth control (except hormonal contraception) or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
- Childbearing potential defined as not being surgically sterilized or have not been free from menses for > 1 year
- Male: use and adequate method of contraception with the first dose of study therapy through 120 days after the last dose of study therapy
- Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
- Absolute neutrophil count (ANC) >= 1500/mm^3 (within 14 days prior to day 1 of protocol therapy)
- Platelets >= 100,000/mm^3 (within 14 days prior to day 1 of protocol therapy)
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (within 14 days prior to day 1 of protocol therapy)
- Serum total bilirubin =< 1.5 x upper limit of normal (ULN) OR direct bilirubin =< ULN if total bilirubin levels > 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)
- Albumin >= 2.5 mg/dL (within 14 days prior to day 1 of protocol therapy)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN OR =< 5.0 x ULN if liver metastases present (within 14 days prior to day 1 of protocol therapy)
- Serum creatinine =< 1.5 x ULN OR creatinine clearance (if measured or calculated per institutional standard; glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min if creatinine levels > 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)
- Female of childbearing potential only: negative urine or serum pregnancy test; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (within 14 days prior to day 1 of protocol therapy)
Who cannot join
- Anti-programmed cell death protein-1 (anti-PD-1), PD ligand-1 (PD-L1), PD ligand-2 (PD-L2) agent, an antibody targeting other immuno-regulatory receptors or mechanisms
- Radiotherapy within 14 days prior to day 1 of protocol therapy
- AR targeted agents (including GTx-024, enzalutamide or other AR targeted therapies)
- Investigational agent within 21 days prior to day 1 of protocol therapy
- Hormone replacement therapies (estrogens, megestrol acetate) within 14 days prior to day 1 of protocol therapy
- Live-virus vaccination within 30 days prior to day 1 of protocol therapy
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- Systemic cytotoxic chemotherapy, antineoplastic biologic therapy, or major surgery within 21 days of the first dose of trial medication
- Testosterone or testosterone-like agents (methyltestosterone, oxandrolone, oxymetholone, danazol, fluoxymesterone, dehydroepiandrosterone, androstenedione) other androgenic compounds or anti-androgens within 30 days prior to day 1 of protocol therapy
- Chronic systemic steroid therapy or on any other form of immunosuppressive medication
- Unstable or untreated brain/leptomeningeal metastasis
- Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)
- Active central nervous system metastases and/or carcinomatous meningitis
- Severe hypersensitivity reaction to treatment with another monoclonal antibody
- Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapies for hormone deficiencies are allowed)
- Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C
- History of pneumonitis (non-infectious) that required steroids or current pneumonitis
- Diagnosed with or treated for cancer within the previous two years, other than breast cancer or non-melanoma carcinoma of the skin
- Unable to swallow capsules
- Currently on bisphosphonate or denosumab with elevated serum calcium levels corrected for albumin/ionized calcium levels outside of institutional normal limits
- Female: pregnant or lactating
- 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)
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
City of Hope Corona
Corona, California, 92879
City of Hope Medical Center
Duarte, California, 91010
City of Hope Antelope Valley
Lancaster, California, 93534
City of Hope Mission Hills
Mission Hills, California, 91345
City of Hope Rancho Cucamonga
Rancho Cucamonga, California, 91730
City of Hope South Pasadena
South Pasadena, California, 91030
City of Hope West Covina
West Covina, California, 91790
About this study
Official title: A Phase 2 Clinical Trial of the Combination of Pembrolizumab and Selective Androgen Receptor Modulator (SARM) GTX-024 in Patients With Metastatic Androgen Receptor (AR) Positive Triple Negative Breast Cancer (TNBC)
This phase II trial studies the side effects and how well pembrolizumab and enobosarm work in treating patients with androgen receptor positive triple negative breast cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Androgen can cause the growth of breast cancer cells. Hormone therapy using enobosarm may fight breast cancer by blocking the use of androgen by the tumor cells. Giving pembrolizumab and enobosarm may work better than pembrolizumab alone in treating patients with androgen receptor positive triple negative breast cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety/tolerability of the combination regimen. II. To determine the response rate (complete response [CR] or partial response [PR] via Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) of the combination of pembrolizumab with enobosarm (GTx-024) in patients with advanced androgen receptor (AR) positive (+) triple negative breast cancer (TNBC).
SECONDARY OBJECTIVES:
- To evaluate clinical outcomes by RECIST 1.1 including clinical benefit rate (CBR) at 24 weeks, progression free-survival (PFS), duration of response (DOR), event free survival (EFS), time-to-treatment failure (TTF); and overall survival (OS).
II. To evaluate the role of immune-related response criteria (irRECIST). III. To evaluate the association of AR by immunohistochemistry (IHC) and clinical response.
EXPLORATORY OBJECTIVES:
- To evaluate the association of an AR gene expression signature and clinical response.
II. To evaluate genomic and phenotypic status of breast tumor. III. To evaluate the effect of the combination therapy on peripheral blood circulating tumor cells (CTCs) and circulating tumor deoxyribonucleic acid (DNA) (ctDNA).
IV. To evaluate the effect of combination therapy on tumor-derived exosomes (TEX) and TEX associated immune biomarkers.
- Immune correlatives:
Va. To evaluate pre-treatment programmed death ligand 1 (PD-L1) and tumor infiltrating lymphocytes (TILs) as a predictor of response to combination therapy.
Vb. To evaluate specific TIL subsets (e.g. CD4, CD8, regulatory T cell [Treg] distribution) and other immunological correlatives (e.g. T cell receptor [TCR] repertoire analysis) as possible predictors of response.
Vc. To evaluate change in TILs as a result of the combination therapy. Vd. To evaluate peripheral blood, immune biomarkers.
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and enobosarm orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days, every 3 months, and bi-annually.
- Conditions
- Androgen Receptor Positive, Estrogen Receptor Negative, HER2/Neu Negative, Metastatic Triple-Negative Breast Carcinoma, Progesterone Receptor Negative, Stage IV Breast Cancer AJCC v6 and v7
- Being tested
- Enobosarm, Laboratory Biomarker Analysis, Pembrolizumab
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnobosarmDrug
Also called Gtx-024, Ostarine
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pembrolizumab, enobosarm) | Experimental | Patients receive pembrolizumab IV over 30 minutes on day 1 and enobosarm PO QD on days 1-21. Courses repeat every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Enobosarm; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate (Complete Response or Partial Response)
Response rate (complete response or partial response) assessed using Response Evaluation Criteria in Solid Tumors version 1.1.
Measured: Up to 36 months
Secondary outcomes (4)
Progression-free Survival
Progression-free survival assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Kaplan-Meier estimates will be generated.
Measured: Time to disease progression/relapse or death as a result of any cause, assessed up to 36 months
Clinical Benefit Rate
Clinical benefit rate assessed by immune-related Response Evaluation Criteria in Solid Tumors version 1.1.
Measured: At 16 weeks
Overall Survival
Overall survival assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Kaplan-Meier estimates will be generated.
Measured: Time to death as a result of any cause, assessed up to 36 months
Progression-free Survival
Progression-free survival defined as failure of treatment or death as a result of any cause assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Kaplan-Meier estimates will be generated.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2016 (estimated)
- Study start1 Jun 2017
- Primary completion28 Oct 2020
- Study completion16 Aug 2022
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.
- Other trials for Androgen Receptor PositiveStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Yuan Yuan, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02971761
- Sponsor's protocol ID
- 16131
- Other IDs
- NCI-2016-01759, 16131
- Status last verified
- Feb 2024
- First submitted
- 21 Nov 2016
- Last updated
- 20 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No