A Study to Evaluate Changes in Human Breast Cancer Tissue Following Short-Term Use of Darolutamide

NCT03004534 | Completed Early Phase 1 Results FDA Drug

• 3 other identifiers: TRIO0302016-004151-79HC6-24-c 201058
• Study Type: interventional
• Target: 36
• Locations: 3 countries
• Sites: 14

Brief Summary

The purpose of this study is to evaluate the effect of short-term treatment with darolutamide on breast cancer cells (i.e., how the treatment may change the genes or proteins in breast cancer cells) and to evaluate its safety and the way it is tolerated by subjects. The intent is to study these changes in order to have a better understanding of the potential use of darolutamide for women with EBC, know which patients are likely or unlikely to respond to this treatment, and determine how darolutamide may be combined with other anti-cancer drugs.

Conditions

Breast Cancer Female

Keywords

Breast Cancer; Breast Carcinoma; Breast Tumours; Early Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Identifying Molecular Alterations in Breast Cancer Tissue Tumor Samples Following Short-Term Preoperative Exposure to Darolutamide in Female Patients Wit Early Breast Cancer.

  Androgen Receptor (AR) was assessed on the collected samples.

  1 year, 6 months

Secondary Outcomes (1)

• Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03

  1 year, 6 months

Study Arms (1)

Presurgical Molecular Assessment

EXPERIMENTAL

Oral 300 mg darolutamide tablet; dose of 600 mg (2 x 300 mg tablets) b.i.d.

Drug: darolutamide

Interventions

darolutamide DRUG

Oral 300 mg tablets; 600 mg (2 x 300 mg tablets) taken twice per day, to a daily dose of 1200 mg.

Also known as: BAY 1841788, ODM-201

Presurgical Molecular Assessment

Eligibility Criteria

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

You may qualify if:

• Signed and dated PICF obtained prior to initiation of any study-specific procedure and treatment.
• Female ≥ 18 years old.
• Histologically proven invasive breast carcinoma (through either a core needle biopsy or an incisional biopsy) for which surgery is indicated as the primary treatment modality. Patients for which Neoadjuvant Systemic Therapy (NAST) is indicated are also eligible provided they are willing to undergo a biopsy after completing treatment with darolutamide and prior to NAST start.
• Known ER, PgR and HER2 statuses.
• Tumor must be confined to either the breast or to the breast and ipsilateral axilla (Note: patinets with multifocal/multicentric tumors are eligible). Patient must have (according to TNM 7th edition rules):
• T1 with T ≥1.0cm, T2 or T3 by at least one radiographic or clinical measurement
• Either clinically positive (N1 only) or clinically negative axillary nodes (N0)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Adequate organ function within 28 days prior to enrollment, as defined by the following criteria:
• Hematology: Hemoglobin ≥ 9.0 g/dl; ANC ≥ 1.5 × 109/L; Platelet count ≥ 100 × 109/L
• Liver function: ALT and AST ≤ 2.5 × ULN; Total bilirubin ≤ 1.5 × ULN (or ≤ 3 times ULN for patients with documented Gilbert's syndrome or for whom indirect bilirubin concentrations suggest an extra-hepatic source of elevation)
• Renal function: Creatinine ≤ 2.0 × ULN
• No more than 42 days should elapse from the day study-specific tumor sample is taken at initial diagnosis (or subsequent procedure) to the day of the first intake of darolutamide.
• Women of childbearing potential (WoCBP)\* must agree to use acceptable non-hormonal contraceptive methods of birth control from the day of the screening pregnancy test and up to 3 months after the last intake of darolutamide.
• For WoCBP\* negative serum pregnancy test within 7 days of enrollment.

You may not qualify if:

• Any T0, Tis, T1 \< 1.0 cm, T4; or N2-3; or M1 BC.
• Bilateral invasive BC.
• Patient that underwent excisional biopsy of the primary tumor.
• Medical indication or patient desire to undergo BC surgery or start NAST prior to completing at least 14 days of treatment with darolutamide, and or refusal of patient to undergo corresponding biopsy in case NAST is planned.
• Prior or concurrent systemic anticancer therapy for BC treatment(immunotherapy, hormonotherapy, biologic/targeted therapy, chemotherapy, investigational agents).
• Prior or concurrent ipsilateral radiation therapy for invasive or noninvasive BC.
• Prior or concurrent treatment or preventative use of any hormonal agent such as aromatase inhibitors (AI), fulvestrant, raloxifene, tamoxifen or other SERM, or with any other hormonal agent used for the treatment or prevention of BC or for any other indication (e.g. osteoporosis).
• Concurrent use of ovarian hormone replacement therapy. Prior treatment should be stopped at least 28 days prior to registration.
• Prior or concurrent treatment with AR antagonists or CYP17 enzyme inhibitor.
• Use of other investigational drug within 28 days of enrollment.
• Major surgery\* within 28 days before enrollment.
• Any concurrent or previous malignancy within 5 years prior to enrollment except for basal or squamous skin cancer, or carcinoma in situ of the cervix, or other non-invasive/in-situ neoplasm, all of which must have been adequately and radically treated. A patient with previous history of invasive malignancy (other than adequately and radically treated basal or squamous skin cancer) is eligible provided that she has been disease free for more than 5 years.
• Severe or uncontrolled concurrent disease, infection or comorbidity.
• Known active viral hepatitis, HIV or chronic liver disease.
• Other serious illness or medical condition within 6 months before enrollment, including any of the following: Concurrent congestive heart failure NYHA Class III or IV, severe/unstable angina pectoris, myocardial infarction, uncontrolled hypertension, coronary/peripheral artery bypass graft, high-risk uncontrolled arrhythmias, stroke.

Sponsors & Collaborators

• Translational Research in Oncology: lead
• Bayer: collaborator

Study Sites (14)

UCLA

Los Angeles, California, 90095-1678, United States

Location

Valley Breast Care and Women's Health Center

Los Angeles, California, 91405, United States

Location

Torrance Memorial Physician Network, Cancer Care Associates

Redondo Beach, California, 90277, United States

Location

Central Coast Medical Oncology

Santa Maria, California, 93454, United States

Location

UF Health Cancer Center - Orlando Health

Orlando, Florida, 32806, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G1Z2, Canada

Location

(CIUSSS) de l'Est-de-l'Île-de-Montréal - l'Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

McGill University Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Centre Hospitalier Affilie Universitaire De Quebec - Hospital Du Saint-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Universitatsklinikum Erlangen

Erlangen, 91054, Germany

Location

Interdisziplinares Onkologisches Zentrum

München, 80336, Germany

Location

Department of Women's Health

Tübingen, 72076, Germany

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

darolutamide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Director, Project Management
• Organization: Translational Research In Oncology (TRIO)

030@trioncology.org

33 158 10 09 09

Study Officials

• Rodrigo Fresco, MD

  Translational Research in Oncology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2016
• First Posted: December 29, 2016
• Study Start: September 5, 2017
• Primary Completion: February 14, 2019
• Study Completion: March 13, 2019
• Last Updated: April 3, 2020
• Results First Posted: April 3, 2020

Record last verified: 2020-03

Locations

US (5); CA (6); DE (3)