Abiraterone acetate in Molecular Apocrine breast cancer

• Register: EUCTR
• Last refreshed on: 12 October 2015
• Main ID: EUCTR2012-002525-29-FR
• Date of registration: 18/04/2013
• Prospective Registration: No
• Primary sponsor: UNICANCER
• Public title: Abiraterone acetate in Molecular Apocrine breast cancer
• Scientific title: A phase II trial evaluating the Activity of Abiraterone Acetate plus Prednisone in Patients with a Molecular Apocrine HER2-negative locally advanced or metastatic Breast Cancer. - AMA
• Date of first enrolment: 08/03/2013
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002525-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

France

Contacts

• Name: Christine ORSINI
• Affiliation: UNICANCER

• Name: Christine ORSINI
• Affiliation: UNICANCER

Key inclusion & exclusion criteria

Inclusion criteria:
1) Women aged = 18 years,
2) Histologically confirmed locally advanced or metastatic breast cancer,
3) Triple negative breast cancer:
Estrogen receptor (ER)-negative and Progesteron receptor (PR)-negative, as defined by a < 10 % tumour 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 either primary or metastatic breast cancer site*,


* In case of discordant ER and/or PR status between the primary tumour and the metastatic site, the status of the metastatic site will be used to decide whether the patient would be eligible or not
4) Androgen receptor (AR)-positive, as defined centrally by a = 10% tumour stained cells by IHC (AR assessment by local pathologist before inclusion is not mandatory),
5) Patients could be chemotherapy naïve (provided they are not presenting with life-threatning metastasis) or have received any number of previous lines of chemotherapy (providing their life expectancy is = 3 months),
6) Pre and post menopausal patients are eligible. In the exceptional situation of a premenopausal patient, the addition of LHRH analog is recommended (androgens might act as an estrogen antagonist in premenopausal patients),
7) Measurable or non measurable disease according to RECIST v1.1 criteria,
8) PS (ECOG) = 2,
9) Normal haematological function: ANC = 1,500/mm3; platelets count = 100,000/mm3; haemoglobin > 10 g/dl,
10) Normal hepatic function: total bilirubin = 1.5 upper normal limit (UNL); ASAT and ALAT = 2.5 UNL (= 5 UNL in the presence of liver metastases),
11) Creatinine clearance (MDRD formula) = 50 mL/min OR creatinine = 1.5 times ULN,
12) Normal kalemia (serum potassium = 3.5mM), natremia and magnesaemia,
13) Systolic blood pressure (BP) < 160 mm Hg and diastolic BP < 95 mm Hg, as documented on inclusion day (Hypertension at baseline assessment allowed provided it is currently controlled under anti-hypertensive drugs),
14) Cardiac ejection fraction =50% measured by MUGA or ECHO done within 4 weeks before inclusion,
15) If receiving a bisphosphonate or denosumab, dose must have been stable for at least 2 doses before inclusion,
16) Patient agreeing to use effective contraception during and for = 6 months after completion of study treatment,
17) Patient able to comply with the protocol,
18) Patient must have signed a written informed consent form prior to any study specific procedures,
19) 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 31
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion criteria:
1) Male breast cancer,
2) HER2-positive status (positivity defined as IHC3+ and/or FISH amplification >2.2),
3) 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,
4) 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,
5) Non-malignant systemic disease, including active infection or concurrent serious illness that would make the patient a high medical risk,
6) Significant cardiovascular disease, including any of the following:
a) NYHA class III-IV congestive heart failure
b) Unstable angina pectoris or myocardial infarction within the past 6 months
c) Severe valvular heart disease
d) Ventricular arrhythmia requiring treatment,
7) Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not be included,
8) Persistent toxicities = grade 2 from any cause, except chemotherapy-induced alopecia and Grade 2 peripheral neuropathy,
9) Active or uncontrolled autoimmune disease requiring concurrent corticosteroid therapy,
10) Any gastrointestinal disorder interfering with absorption of the study drug,
11) Difficulties with swallowing study capsules,
12) Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy, chemotherapy (CT) within the last 3 weeks (2 weeks for oral or weekly CT ; 6 weeks for nitrosoureas and mitomycin C), or other investigational agents ; Concurrent palliative radiotherapy allowed,
13) Concurrent enrolment in another clinical trial in which investigational therapies are administered,
14) Pregnant women, women who are likely to become pregnant or are breast-feeding,
15) 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,
16) Patients with history of non compliance to medical regimens or unwilling or unable to comply with the protocol,
17) Individual deprived of liberty or placed under the authority of a tutor.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Molecular apocrine locally advanced or metastatic breast cancer
MedDRA version: 14.1 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: Zytiga
Pharmaceutical Form: Tablet
INN or Proposed INN: ABIRATERONE ACETATE
CAS Number: 154229-18-2
Other descriptive name: ABIRATERONE ACETATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Primary end point(s): Clinical benefit rate (CBR) :
The 6-months CBR is the measurement of all patients who have a complete response (CR), partial response (PR) or stable disease (SD), according to RECIST criteria v1.1.

Secondary Objective: - Objective response rate (ORR)
- Duration of overall response (DoR).
- Overall survival (OS)
- Progression-free survival (PFS)
- Tolerance and safety of abiraterone acetate.

Main Objective: To estimate antitumor activity of abiraterone acetate, as measured by the 6 months clinical benefit rate (CBR) in molecular apocrine HER2-negative locally advanced or metastatic breast cancer.

Secondary Outcome(s)

Secondary end point(s): Efficacy:
- Objective response rate (ORR)
The Objective response is defined as complete response (CR) or partial response (PR) according to RECIST criteria v1.1.
- Duration of overall response (DoR)
The DoR is defined as the time from documentation of tumour response (CR/PR) to disease progression, according to RECIST criteria v1.1.
- Overall Survival (OS)
The OS is defined as the time from the first administration of abiraterone acetate to death from any cause.
- Progression-free survival (PFS)
The PFS is defined as the time from the first administration of abiraterone acetate to progression (or death of any cause, whichever occurs first


Safety:
- Evaluation of Toxicity
Safety will be evaluated by type, frequency and severity of adverse drug reactions according to NCI-CTC (v4.0): In order to be considered evaluable for toxicity, patients should have received at least one dose of treatment.

Secondary ID(s)

UC-0140/1206

Source(s) of Monetary Support

Laboratory JANSSEN