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

• Sponsor: Veru Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04869943
• Collaborator: (none)
• Enrollment: 210
• Locations: 59
• Arms: 2
• Anticipated Duration (Months): 18.6
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Enobosarm; Drug: Exemestane	Phase 3

Detailed Description

This study is a multicenter, randomized, open-label, two treatment arm, efficacy and safety study. Subjects will be randomized to the two treatment arms in a 1:1 fashion. The primary efficacy endpoint of the study will be the median rPFS. Subjects will continue study treatment until disease progression is observed or an unacceptable adverse event is observed. A safety follow up visit will occur approximately 30 days after last dose of study drug. Thereafter, survival follow up will 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 210 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects in the Enobosarm Treatment Group will receive enobosarm 9mg each day by mouth until disease progression or an unacceptable adverse event is observed. Subjects in the Control Treatment Group will receive a 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.Subjects in the Enobosarm Treatment Group will receive enobosarm 9mg each day by mouth until disease progression or an unacceptable adverse event is observed. Subjects in the Control Treatment Group will receive a 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Crossover Ph3 to Evaluate Efficacy/Safety of Enobosarm Monotherapy vs Active Control for Treatment of AR+/ER+/HER2- MBC With AR Staining ≥40% Previously Treated w/Nonsteroidal Aromatase Inhibitor, SERD & CDK 4/6 Inhibitor
• Actual Study Start Date: Oct 12, 2021
• Anticipated Primary Completion Date: Mar 30, 2023
• Anticipated Study Completion Date: Apr 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Enobosarm; Oral Enobosarm 9mg per day; Other Names: VERU-024
Active Comparator: 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.	Drug: Exemestane; Exemestane monotherapy, exemestane plus everolimus, or selective estrogen receptor modulator (SERM); Other Names: Mestane

Outcome Measures

Primary Outcome Measures

1. To demonstrate the efficacy of Enobosarm in the treatment of androgen receptor positive (AR+) and estrogen receptor positive (ER+) metastatic breast cancer (MBC) as measured by radiographic progression free survival (rPFS). [Day 120]

   The primary endpoint for the study is the median radiographic progression free survival (rPFS) in the Enobosarm Treatment Group compared to the Control Treatment Group. Progression will be defined based on RECIST 1.1.

Secondary Outcome Measures

1. Objective Response Rate (ORR) [Day 180]

   Objective Response Rate (ORR), proportion of subjects with a best tumor response of ORR (PR or CR) on study

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Oncology and Hematology, LLC.	Anchorage	Alaska	United States	99508
2	Ironwood Cancer and Research Centers	Chandler	Arizona	United States	85224
3	Banner Health/ Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
4	The Oncology Insitute of Hope and Innovation	Glendale	California	United States	91204
5	Marin Cancer Care, Inc.	Greenbrae	California	United States	94904
6	California Research Institute (CRI)	Los Angeles	California	United States	90027
7	University of California San Francisco Comprehensive Cancer Center	San Francisco	California	United States	94158
8	Providence Medical Group	Santa Rosa	California	United States	95043
9	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
10	GenesisCare USA	Aventura	Florida	United States	33180
11	Morton Plant Hospital/ BayCare Health System, Inc	Clearwater	Florida	United States	33756
12	University of Miami- Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33146
13	Miami Cancer Institute	Miami	Florida	United States	33176
14	Woodlands Medical Specialists, PA	Pensacola	Florida	United States	32503
15	Miami Cancer Institute, Plantation MCIP	Plantation	Florida	United States	33324
16	University Cancer & Blood Center	Athens	Georgia	United States	30607
17	Blessing Corporate Services	Quincy	Illinois	United States	62301
18	MBCCOP - LSU Health Sciences Center	Shreveport	Louisiana	United States	71103
19	Dana-Farber Cancer Institute Breast Oncology	Boston	Massachusetts	United States	02215
20	Revive Research Institute	Farmington Hills	Michigan	United States	48073
21	Sikar Grewal	Sterling Heights	Michigan	United States	48314
22	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
23	Astera Cancer Care	East Brunswick	New Jersey	United States	08816
24	Inspira Medical Center Mullica Hill	Mullica Hill	New Jersey	United States	08062
25	Inspira Medical Center	Vineland	New Jersey	United States	08360
26	The Lindner Center for Research and Education at the Christ Hospital	Cincinnati	Ohio	United States	45219
27	Magee-Women's Hospital	Pittsburgh	Pennsylvania	United States	15219
28	Tidelands Health	Murrells Inlet	South Carolina	United States	29576
29	Tennessee Cancer Specialists	Knoxville	Tennessee	United States	37909
30	Baptist Clinical Research Institute	Nashville	Tennessee	United States	38102
31	Texas Oncology Sammons Cancer Center	Dallas	Texas	United States	75246
32	Texas Oncology - Tyler	Tyler	Texas	United States	75702
33	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
34	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
35	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia	United States	24014
36	MultiCare Institute for Research and Innovation	Puyallup	Washington	United States	98372
37	University of Washington	Seattle	Washington	United States	98109
38	Cancer Care Northwest	Spokane	Washington	United States	99216
39	MultiCare Institute for Research and Innovation	Spokane	Washington	United States	99218
40	Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli	Lublin		Poland	20-090
41	Specjalistyczny Szpital Onkologiczny NU-MED	Maków Mazowiecki		Poland	97-200
42	"Oddział Onkologii Klinicznej i Chemioterapii Europejskie Centrum Zdrowia Otwock"	Otwock		Poland	05-400
43	Klinika Nowotworów Piersi i Chirurgii Rekonstrukcyjnej, Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy	Warsaw		Poland	02-781
44	Wojewódzka Przychodnia Onkologiczna, Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi	Łódź		Poland	91-211
45	Instytut Centrum Zdrowia Matki Polki	Łódź		Poland	93-338
46	A Coruña University Hospital	A Coruña		Spain
47	Hospital Universitari Dexeus	Barcelona		Spain	08028
48	Hospital Universitari Vall d'Hebron - Vall d'Hebron Institut d'Oncologia (VHIO)	Barcelona		Spain	08035
49	Institut Catala d'Oncologia (ICO)	Barcelona		Spain	08908
50	Hospital Universitari Arnau de Vilanova de Lleida	Lleida		Spain	25198
51	Hospital Ruber Internacional	Madrid		Spain	28034
52	Hospital Universitario 12 de Octubre (H12O)	Madrid		Spain	28041
53	Hospital Universitario HM Sanchinarro	Madrid		Spain	28050
54	Hospital Clínico Universitario de Valencia (CHUV)	Valencia		Spain	46010
55	Municipal Institution "Dnipropetrovsk City Multi-field Clinical Hospital #4", Dnepropetrovsk state m	Dnepropetrovsk		Ukraine	49000
56	State institution "V.T. Zaycev Institute of general and urgent surgery of National academy medical sciences of Ukraine"	Kharkiv		Ukraine	61103
57	Khmelnytsky Regional Antitumor Center, Department of Breast, Skin, Soft Tissues and Bones Tumorsa	Khmelnytskyi		Ukraine	29000
58	Kyiv City Clinical Oncology Center	Kyiv		Ukraine	03115
59	Odessa Regional Oncological Dispensary	Odessa		Ukraine	65000

Sponsors and Collaborators

• Veru Inc.

Investigators

• Study Chair: Barnette, Veru Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Veru Inc.
• ClinicalTrials.gov Identifier: NCT04869943
• Other Study ID Numbers: V3002401
• First Posted: May 3, 2021
• Last Update Posted: Aug 24, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Veru Inc.: Third line; 3rd line; Androgen Receptor
• Additional relevant MeSH terms: Breast Neoplasms; Exemestane

Study Results

No Results Posted as of Aug 24, 2022