Phase 1

• Conditions: Triple-negative androgen receptor positive (molecular apocrine-like HER2-negative subtype) locally advanced (unresectable) or metastatic breast cancer.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-002284-18-FR
• Lead Sponsor: ICANCER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-10-20
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 90

Inclusion Criteria

1) Woman = 18 years old;
2) Histologically confirmed locally advanced (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 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 RECIST v1.1;
8) ECOG = 1;
9) Normal hematological function: 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; ASAT and ALAT = 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 MUGA or 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

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 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:
a) NYHA class III-IV congestive heart failure
b) Stroke, unstable angina pectoris, or myocardial infarction within the past 6 months
c) Severe valvular heart disease
d) 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) Active or uncontrolled autoimmune disease requiring concurrent corticosteroid therapy;
9) Any gastrointestinal disorder interfering with absorption of the study drug;
10) Difficulties with swallowing tablets;
11) An active viral hepatitis, known human immunodeficiency virus infection with detectable viral load, or chronic liver disease requiring treatment;
12) Previous treatment with second–generation AR inhibitors such as enzalutamide, ARN–509,
darolutamide, other investigational AR inhibitors CYP17 enzyme inhibitor such as abiraterone, capecitabine…
13) Capecitabine is contraindicated for patients with known deficit of dihydropyrimidine dehydrogenase (DPD) activity;
14) Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy; chemotherapy within the last 3 weeks (6 weeks for nitrosoureas and mitomycin C), or other investigational agents; concurrent palliative radiotherapy is allowed;
15) Concurrent enrolment in another clinical trial in which investigational therapies are administered;
16) Pregnant women, women who are likely to become pregnant or are breast-feeding;
17) 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;
18) Patients with history of non-compliance to medical regimens or unwilling or unable to comply with the protocol;
19) Individual deprived of liberty or placed under the authority of a tutor.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified