Efficacy Evaluation of Enobosarm Monotherapy in Treatment of AR+/ER+/HER2- Metastatic Breast Cancer

NCT ID: NCT04869943

Last Updated: 2024-01-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-12
• Study Completion Date: 2024-01-09

Brief Summary

To demonstrate the efficacy of enobosarmin the treatment of androgen receptor positive (AR+) and estrogen receptor positive (ER+) metastatic breast cancer (MBC) as measured by radiographic progression free survival (rPFS).

Detailed Description

This study is a multicenter, randomized, open-label, two treatment arm, efficacy and safety study, comprised of two sections, the main study and the post-study extension period. Subjects will be randomized to the two treatment arms in a 1:1 fashion (into the main study), with the opportunity for subjects initially randomized to the Control Treatment Group to cross over to receive the investigational treatment in the post-study extension period.

The primary efficacy endpoint of the study will be the median rPFS. Subjects will continue study treatment until disease progression confirmed by blinded independent central reader (BICR) is observed. A safety follow up visit will occur approximately 30 days after last dose of study drug. Thereafter, survival follow up will be completed monthly for one year. Survival follow up may be completed by phone or records review. After one year, survival follow up will be completed every 90 days.

After radiographic progression (by RECIST 1.1) is confirmed by blinded independent central reader (BICR) and have received approval from Medical Monitor, subjects in the Control Treatment Group may be crossed over to receive enobosarm treatment (9mg per day). Treatment will continue in this population (Enobosarm Post-study Group (EPG)) until radiographic progression (by RECIST 1.1), confirmed by BICR, is observed. The efficacy database for this crossover group will be completely separate from the main portion of the study and the data will be analyzed separately.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Enobosarm Treatment Group

Subjects in the Enobosarm Treatment Group will receive enobosarm 9mg each day by mouth until disease progression or an unacceptable adverse event is observed. The total duration of the study for a subject in the study from screening to follow-up visit is not standardized and will be different for each subject.

Group Type: EXPERIMENTAL

Enobosarm

Intervention Type: DRUG

Oral Enobosarm 9mg per day

Control Treatment Group

Subjects in the Control Treatment Group will receive an ER targeted therapy limited to exemestane monotherapy, exemestane plus everolimus or selective estrogen receptor modulator (SERM) approved for the treatment of breast cancer and is part of the standard of care at the clinical study site. The decision of which comparator treatment will be used will be made prior to randomization. After radiographic progression, subjects randomized to the Control Treatment Group may be crossed over to receive enobosarm 9mg.

Group Type: ACTIVE_COMPARATOR

Exemestane

Intervention Type: DRUG

Exemestane monotherapy, exemestane plus everolimus, or selective estrogen receptor modulator (SERM)

Interventions

Enobosarm

Oral Enobosarm 9mg per day

Intervention Type: DRUG

Exemestane

Exemestane monotherapy, exemestane plus everolimus, or selective estrogen receptor modulator (SERM)

Intervention Type: DRUG

Other Intervention Names

VERU-024; Mestane

Eligibility Criteria

Inclusion Criteria

• Provide informed consent
• Be able to communicate effectively with the study personnel
• Aged ≥18 years
• For Female Subjects

• Menopausal status
• Be postmenopausal as defined by the National Comprehensive Cancer Network as either:

• 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
• Be premenopausal or perimenopausal on ovarian suppression with LHRH agonist for at least 4 months, with an estradiol assay <20 pg/mL and a negative urine pregnancy test.
• If subject is of child bearing potential, the subject must agree to use acceptable methods of contraception:

• If female study participant could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository [i.e., barrier method of contraception], surgical sterilization of male partner (vasectomy with documentation of azoospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}
• If female study participant has undergone documented tubal ligation (female sterilization), a barrier method (condom used with spermicidal foam/gel/film/cream/suppository) should also be used
• If female study participant has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with spermicidal foam/gel/film/cream/suppository) should also be used
• For Male Subjects

• Subject must agree to use acceptable methods of contraception:
• If the study subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/ film/cream/suppository [i.e., barrier method of contraception], surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom used with spermicidal foam/gel/film/cream/suppository)
• If female partner of a study subject has undergone documented tubal ligation (female sterilization), a barrier method (condom used with spermicidal foam/gel/film/cream/suppository) should also be used
• If female partner of a study subject has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with spermicidal foam/gel/film/cream/suppository) should also be used
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
• Documented evidence of ER+/HER2- metastatic breast cancer
• Measurable disease is required as per RECIST 1.1 (NOTE: Bone only metastatic disease is acceptable but requires a measurable component
• Have androgen receptor nuclei staining ≥40% as assessed by central laboratory
• Received at least 2 prior lines of treatment in MBC setting which must have included both an AI (monotherapy or combination) and fulvestrant (monotherapy or combination); at least one must have been given in combination with a CDK 4/6 inhibitor.
• Previously responded (without disease progression for at least 6 months) to one of the following treatments: fulvestrant monotherapy or fulvestrant plus CDK 4/6 inhibitor or nonsteroidal aromatase inhibitor monotherapy or nonsteroidal aromatase inhibitor plus CDK 4/6 inhibitor for metastatic breast cancer.
• Subject is willing to comply with the requirements of the protocol through the end of the study

Exclusion Criteria

• Known hypersensitivity or allergy to enobosarm
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 X upper limit of normal (ULN) or total bilirubin >ULN (an elevated total bilirubin up to 1.5 X ULN attributed to a previously confirmed diagnosis of Gilbert's disease is acceptable if all other eligibility criteria are met). In patients with documented metastases to the liver, the limits for inclusion are ALT or AST >5.0 X ULN or total bilirubin >1.5 X ULN.
• Patients with biliary catheter.
• Creatinine clearance < 30 mL/min as measured using the Cockcoft Gault formula (patients with mild and moderate renal failure are not excluded from participation in this study)
• Previously received >1 course of systemic chemotherapy (not including immunotherapies or targeted therapies) for the treatment of metastatic breast cancer.

Note: Subjects may have received 1 course of chemotherapy in the adjuvant or neoadjuvant setting would not count as a line of therapy.

• 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 30 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
• Any comorbid disease or condition (medical or surgical) which might compromise the hematologic, cardiovascular, endocrine, pulmonary, severe renal impairment, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk
• Treatment with any investigational product within < 4 half-lives for each individual investigational product OR within 30 days prior to randomization
• Major surgery within 30 days prior to randomization
• Treatment with testosterone, methyltestosterone, oxandrolone (Oxandrin®), oxymetholone, danazol, fluoxymesterone (Halotestin®), testosterone-like agents (such as dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or antiandrogens (enzalutamide, abiraterone, bicalutamide, apalutamide, or darolutamide). Previous therapy with testosterone and testosterone-like agents is acceptable with a 30-day washout (if previous testosterone therapy was long term depot within the past 6 months, the site should contact the Medical Monitor) or any other androgenic agent.
• Treatment with any of the following hormone replacement therapies for metastatic breast cancer. Prior use in the adjuvant or neoadjuvant setting is allowed if the treatment is, discontinued greater than 30 days prior to randomization

• Estrogens
• Megesterol acetate
• Testosterone
• All other concurrent anticancer treatments (including, but not limited to, all SERMs unless randomized to the Control Treatment Group with a SERM as the control treatment, AIs unless randomized to Control Treatment Group (exemestane or exemestane plus everolimus) with the AI containing treatment as the control treatment, and all CDK 4/6 inhibitors)
• An abnormal ECG result which, based on the investigator's clinical judgment, would place the subject at increased risk
• Has a known additional, invasive, malignancy that is progressing or required active treatment in the last 5 years [note: subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal breast carcinoma in situ, bladder cancer (superficial treated), or cervical carcinoma in situ that have undergone potentially curative therapy are not excluded]
• Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of study treatment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Veru Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Barnette

Role: STUDY_CHAIR

Veru Inc.

Locations

Ironwood Cancer and Research Centers

Chandler, Arizona, United States

Banner Health/ Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

The Oncology Insitute of Hope and Innovation

Glendale, California, United States

Marin Cancer Care, Inc.

Greenbrae, California, United States

California Research Institute (CRI)

Los Angeles, California, United States

University of California San Francisco Comprehensive Cancer Center

San Francisco, California, United States

Providence Medical Group

Santa Rosa, California, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Morton Plant Hospital/ BayCare Health System, Inc

Clearwater, Florida, United States

University of Miami- Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

Woodlands Medical Specialists, PA

Pensacola, Florida, United States

Miami Cancer Institute, Plantation MCIP

Plantation, Florida, United States

University Cancer & Blood Center

Athens, Georgia, United States

Blessing Corporate Services

Quincy, Illinois, United States

MBCCOP - LSU Health Sciences Center

Shreveport, Louisiana, United States

Dana-Farber Cancer Institute Breast Oncology

Boston, Massachusetts, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Astera Cancer Care

East Brunswick, New Jersey, United States

Inspira Medical Center Mullica Hill

Mullica Hill, New Jersey, United States

Inspira Medical Center

Vineland, New Jersey, United States

The Lindner Center for Research and Education at the Christ Hospital

Cincinnati, Ohio, United States

Magee-Women's Hospital

Pittsburgh, Pennsylvania, United States

Tidelands Health

Murrells Inlet, South Carolina, United States

Tennessee Cancer Specialists

Knoxville, Tennessee, United States

Baptist Clinical Research Institute

Nashville, Tennessee, United States

Texas Oncology Sammons Cancer Center

Dallas, Texas, United States

Texas Oncology - Tyler

Tyler, Texas, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Oncology and Hematology Associates of Southwest Virginia, Inc.

Roanoke, Virginia, United States

MultiCare Institute for Research and Innovation

Puyallup, Washington, United States

Cancer Care Northwest

Spokane, Washington, United States

MultiCare Institute for Research and Innovation

Spokane, Washington, United States

Wojewódzka Przychodnia Onkologiczna, Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi

Lodz, , Poland

Instytut Centrum Zdrowia Matki Polki

Lodz, , Poland

Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli

Lublin, , Poland

Specjalistyczny Szpital Onkologiczny NU-MED

Maków Mazowiecki, , Poland

"Oddział Onkologii Klinicznej i Chemioterapii Europejskie Centrum Zdrowia Otwock"

Otwock, , Poland

Klinika Nowotworów Piersi i Chirurgii Rekonstrukcyjnej, Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy

Warsaw, , Poland

A Coruña University Hospital

A Coruña, , Spain

Hospital Universitari Dexeus

Barcelona, , Spain

Hospital Universitari Vall d'Hebron - Vall d'Hebron Institut d'Oncologia (VHIO)

Barcelona, , Spain

Institut Catala d'Oncologia (ICO)

Barcelona, , Spain

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, , Spain

Hospital Ruber Internacional

Madrid, , Spain

Hospital Universitario 12 de Octubre (H12O)

Madrid, , Spain

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Hospital Clínico Universitario de Valencia (CHUV)

Valencia, , Spain

Municipal Institution "Dnipropetrovsk City Multi-field Clinical Hospital #4", Dnepropetrovsk state m

Dnipro, , Ukraine

State institution "V.T. Zaycev Institute of general and urgent surgery of National academy medical sciences of Ukraine"

Kharkiv, , Ukraine

Khmelnytsky Regional Antitumor Center, Department of Breast, Skin, Soft Tissues and Bones Tumorsa

Khmelnytskyi, , Ukraine

Kyiv City Clinical Oncology Center

Kyiv, , Ukraine

Odessa Regional Oncological Dispensary

Odesa, , Ukraine

Countries

United States; Poland; Spain; Ukraine

Other Identifiers

V3002401

Identifier Type: -

Identifier Source: org_study_id