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

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ClinicalTrials.gov Identifier: NCT03004534
Recruitment Status : Recruiting
First Posted : December 29, 2016
Last Update Posted : October 8, 2018
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Translational Research in Oncology

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Female Drug: darolutamide Early Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Presurgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide (ODM-201)
Actual Study Start Date : September 5, 2017
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : April 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Presurgical Molecular Assessment
Oral 300 mg darolutamide tablet; dose of 600 mg (2 x 300 mg tablets) b.i.d.
Drug: darolutamide
Oral 300 mg tablets; 600 mg (2 x 300 mg tablets) taken twice per day, to a daily dose of 1200 mg.
Other Names:
  • BAY 1841788
  • ODM-201




Primary Outcome Measures :
  1. Explore/Define Molecular Alterations in Core Tissue Tumor Samples Following Darolutamide Administration [ Time Frame: Throughout study completion (14 days of treatment + 30 days to End-of-Study) ]
    The following markers will be assessed on the collected samples (appropriate positive and negative controls will be applied): AR, ER, PgR, HER2, ki67, and Cytokeratins 5 and 6.


Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Throughout study completion (14 days of treatment + 30 days to End-of-Study). ]
    The assessment of safety will be performed for all subjects who have taken at least one tablet of darolutamide (defined as the "safety population")



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed and dated PICF obtained prior to initiation of any study-specific procedure and treatment.
  2. Female ≥ 18 years old.
  3. 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.
  4. Known ER, PgR and HER2 statuses.
  5. 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)
    • M0
  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  7. 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
  8. 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.
  9. 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.
  10. For WoCBP* negative serum pregnancy test within 7 days of enrollment.
  11. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and biopsies as detailed in the protocol.

    • Note: WoCBP are any women between menarche and menopause who have not been permanently sterilized, capable of procreation. Permanent sterilization includes hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal ligation/occlusion. Postmenopause is defined as: Bilateral oophorectomy; Age ≥ 60; Age < 60 and amenorrheic for ≥ 12 months in the absence of an alternative medical cause and FSH and estradiol in postmenopausal ranges.

Exclusion Criteria:

  1. Any T0, Tis, T1 < 1.0 cm, T4; or N2-3; or M1 BC.
  2. Bilateral invasive BC.
  3. Patient that underwent excisional biopsy of the primary tumor.
  4. 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.
  5. Prior or concurrent systemic anticancer therapy for BC treatment(immunotherapy, hormonotherapy, biologic/targeted therapy, chemotherapy, investigational agents).
  6. Prior or concurrent ipsilateral radiation therapy for invasive or noninvasive BC.
  7. 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).
  8. Concurrent use of ovarian hormone replacement therapy. Prior treatment should be stopped at least 28 days prior to registration.
  9. Prior or concurrent treatment with AR antagonists or CYP17 enzyme inhibitor.
  10. Use of other investigational drug within 28 days of enrollment.
  11. Major surgery* within 28 days before enrollment.
  12. 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.
  13. Severe or uncontrolled concurrent disease, infection or comorbidity.
  14. Known active viral hepatitis, HIV or chronic liver disease.
  15. 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.
  16. Any contraindication to oral agents or gastrointestinal disorder or procedure which expects to interfere significantly with absorption of protocol treatment.
  17. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
  18. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  19. Known allergy to darolutamide or any of the excipients.
  20. Pregnant or lactating darolutamide. * Note: Major surgery defined as requiring a general anesthesia or respiratory assistance; involving openings into the great cavities of the body, organs removed, or normal anatomy altered; implying risks of severe hemorrhage; implying risk for life of the patient or severe disability.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03004534


Contacts
Contact: Dennis Slamon, MD (310) 825-5193 dslamon@mednet.ucla.edu

Locations
United States, California
UCLA Recruiting
Los Angeles, California, United States, 90095-1678
Principal Investigator: Dennis Slamon, MD         
Valley Breast Care and Women's Health Center Recruiting
Los Angeles, California, United States, 91405
Principal Investigator: Thomas Lomis         
Torrance Memorial Physician Network, Cancer Care Associates Recruiting
Redondo Beach, California, United States, 90277
Principal Investigator: David Chan, MD         
Central Coast Medical Oncology Completed
Santa Maria, California, United States, 93454
United States, Florida
UF Health Cancer Center - Orlando Health Completed
Orlando, Florida, United States, 32806
Canada, Alberta
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada, T6G1Z2
Principal Investigator: John Mackey, MD         
Canada, Quebec
Centre Hospitalier de l'Université de Montréal (CHUM) Recruiting
Montreal, Quebec, Canada, H2X 3E4
Principal Investigator: Andre Robidoux, MD         
Jewish General Hospital Recruiting
Montreal, Quebec, Canada, H3T1E2
Principal Investigator: Jean-Francois Boileau, MD         
McGill University Hospital Recruiting
Montreal, Quebec, Canada, H4A 3J1
Principal Investigator: Nathaniel Bouganim, MD         
(CIUSSS) de l'Est-de-l'Île-de-Montréal - l'Hôpital Maisonneuve-Rosemont Completed
Montréal, Quebec, Canada, H1T 2M4
Centre Hospitalier Affilie Universitaire De Quebec - Hospital Du Saint-Sacrement Recruiting
Quebec City, Quebec, Canada, G1S 4L8
Principal Investigator: Louise Provencher, MD         
Germany
Universitatsklinikum Erlangen Recruiting
Erlangen, Germany, 91054
Principal Investigator: Peter Fasching, MD         
Interdisziplinares Onkologisches Zentrum Recruiting
Muenchen, Germany, 80336
Principal Investigator: Wolfgang Eiermann, MD         
Department of Women's Health Recruiting
Tubingen, Germany, 72076
Principal Investigator: Andreas Hartkopf, MD         
Sponsors and Collaborators
Translational Research in Oncology
Bayer
Investigators
Study Director: Rodrigo Fresco, MD Translational Research in Oncology

Responsible Party: Translational Research in Oncology
ClinicalTrials.gov Identifier: NCT03004534     History of Changes
Other Study ID Numbers: TRIO030
2016-004151-79 ( EudraCT Number )
HC6-24-c 201058 ( Other Identifier: Health Canada )
First Posted: December 29, 2016    Key Record Dates
Last Update Posted: October 8, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
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 Translational Research in Oncology:
Breast Cancer
Breast Carcinoma
Breast Tumours
Early Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Androgen Receptor Antagonists
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs