Study on Androgen Receptor and Triple Negative Breast Cancer

• Status: Active, not recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: Female

Summary

This is a multicenter uncontrolled, open-label, prospective, non-comparative randomized, phase II study. Patients will be randomized between darolutamide in Arm n°1 (two-stage Simon's design) and capecitabine in Arm n°2 with two patients randomized in Arm n°1 for one patient randomized in Arm n°2.

The trial population is composed of women over 18 years old with triple-negative and androgen receptor positive, locally recurrent (unresectable) or metastatic breast cancer.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: UNICANCER
• Treatments: Capecitabine

Criteria

Inclusion Criteria:

1. Woman, ≥18 years old;

2. Histologically confirmed locally recurrent (unresectable) or metastatic breast cancer;

3. Triple negative breast cancer:

Estrogen receptor (ER)-negative and Progesterone receptor (PgR)-negative, as defined by a <10 % tumor stained cells by immunohistochemistry (IHC); HER2 negative status (i.e. IHC score 0 or 1+, or IHC score 2+ and FISH/SISH/CISH negative), confirmed centrally before inclusion with FFPE tissue from the primary tumour;

4. Androgen receptor (AR)-positive, as defined centrally by a ≥ 10% tumor stained cells by IHC Note: AR assessment by local pathologist before inclusion is not mandatory;

5. Patients with a relapse or progressive disease should be chemotherapy naïve or have received a maximum of one line of chemotherapy for advanced disease (providing they are not presenting with life-threatening metastasis); patients could have received adjuvant or neo-adjuvant therapy;

6. In the exceptional situation of pre-menopausal patient, the addition of a LHRH analog is recommended (androgens might act as an estrogen antagonist in premenopausal patients);

7. Presence of measurable or evaluable disease according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)

8. Eastern cooperative oncology group (ECOG) ≤1;

9. Normal hematological function: Absolute neutrophile count (ANC) ≥1,500/mm³; platelets count ≥100,000/mm³; hemoglobin >10 g/dL; Note: subject must not have received any growth factor within 4 weeks or blood transfusion within 7 days of the hematology laboratory sample obtained at screening)

10. Normal hepatic function: total bilirubin ≤ 1.5 upper normal limit (UNL) unless this increase is due to a known Gilbert's disease; aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤2.5 UNL (or ≤5 UNL in case of hepatic metastasis);

11. Creatinine clearance (MDRD formula) ≥50 mL/min;

12. Systolic blood pressure (BP) <160 mm Hg and diastolic BP <95 mm Hg, as documented on day of registration/consent (Hypertension allowed provided it is currently controlled);

13. Cardiac ejection fraction ≥50% measured by multigated acquisition (MUGA) or echocardiography (ECHO) done within 4 weeks before inclusion;

14. For premenopausal patients, patient agreeing to use effective contraception during and for ≥6 months after completion of study treatment;

15. Patient able to comply with the protocol;

16. Patient must have signed a written informed consent form prior to any study specific procedures;

17. Patient must be affiliated to a Social Health Insurance.

Exclusion Criteria:

1. HER2-positive status (positivity defined as IHC3+ and/or FISH amplification ≥2);

2. Other concurrent malignancies, except adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin; patients who have undergone potentially curative therapy for a prior malignancy are eligible provided there is no evidence of disease for ≥5 years and patient is deemed to be at low risk for recurrence;

3. Active brain metastases or leptomeningeal disease; history of brain metastases allowed provided lesions are stable for at least 3 months as documented by head CT scan or Magnetic resonance Imaging (MRI) of the brain;

4. Non-malignant systemic disease, including active infection or concurrent serious illness that would make the patient a high medical risk;

5. Significant cardiovascular disease, including any of the following:

1. NYHA class III-IV congestive heart failure

2. Stroke, unstable angina pectoris or myocardial infarction within the past 6 months

3. Severe valvular heart disease

4. Ventricular arrhythmia requiring treatment;

6. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not be included;

7. Persistent toxicities grade ≥2 from any cause, except chemotherapy-induced alopecia and grade 2 peripheral neuropathy;

8. Any gastrointestinal disorder interfering with absorption of the study drug;

9. Difficulties with swallowing tablets;

10. An active viral hepatitis, known human immunodeficiency virus infection with detectable viral load, or chronic liver disease requiring treatment;

11. PREVIOUS TREATMENT IN THE METASTATIC SETTING: Previous treatment with: capecitabine (MET SETTING), first generation (bicalutamide) or second-generation AR inhibitors (enzalutamide, ARN-509, darolutamide) or other investigational AR inhibitors CYP17 enzyme inhibitor such as abiraterone (capecitabine in the adjuvant setting is allowed provided the last administration was at least ≥12 months prior to study entry)

12. Patients with known deficit of dihydropyrimidine dehydrogenase (DPD) activity; or in case of hypersensitivity to capecitabine or to any of its excipients or to fluorouracil;

13. Prior anticancer therapy within the last 3 weeks including radiotherapy, endocrine therapy, immunotherapy; chemotherapy (6 weeks for nitrosoureas and mitomycin C), or other investigational agents; concurrent palliative radiotherapy is allowed;

14. Concurrent enrolment in another clinical trial in which investigational therapies are administered;

15. Pregnant women, women who are likely to become pregnant or are breast-feeding;

16. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. Those conditions should be discussed with the patient before registration in the trial;

17. Patients with history of non-compliance to medical regimens or unwilling or unable to comply with the protocol;

18. Individual deprived of liberty or placed under the authority of a tutor.