Abiraterone Acetate in Molecular Apocrine Breast Cancer

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

Sponsors

Lead Sponsor: UNICANCER

Source UNICANCER
Brief Summary

The purpose of this study is to estimate antitumour activity of abiraterone acetate in Patients with a Molecular Apocrine HER2-negative locally advanced or metastatic Breast Cancer.

Detailed Description

Screening : All women 18+, with a confirmed locally advanced or metastatic Triple Negative Breast Cancer (TNBC), will be screened and invited to participate (300-500 patients).

Only patients with a centralized confirmation of ER-/PR-/HER2- and evaluation of AR+ will be included and treated with abiraterone acetate plus prednisone (31 patients).

The Treatment phase comprises a series of 4 weeks-cycles with continuous study treatment. Study drug treatment will continue until the earliest of the following events: disease progression, unacceptable toxicity, or death.

At disease progression, patients must be discontinued from study drug and should be evaluated within 30 days during the Post treatment visit and then entered into the Follow-Up phase.Patients should enter the Follow-Up Period regardless of reason for study drug discontinuation and should be monitored every 3 months (± 7 days) during 2 years.

Overall Status Active, not recruiting
Start Date July 2013
Completion Date February 2021
Primary Completion Date July 2015
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Clinical benefit rate (CBR) at 6 months
Secondary Outcome
Measure Time Frame
Objective response rate (ORR) at 6 months
Duration of overall response (DoR) at 6 months
Overall Survival (OS) median follow-up = 2 years
Progression-free survival (PFS) median follow-up = 2 years
Overall safety profile during the on-treatment period (defined as the period from the time of first dose of study medications up to 30 days of the last dose)
Enrollment 31
Condition
Intervention

Intervention Type: Drug

Intervention Name: Abiraterone Acetate

Description: Patients will receive abiraterone acetate at 1,000 mg (four 250 mg tablets daily in the morning after an overnight fast) concurrently with prednisone(1) at 10 mg once daily.

Arm Group Label: Abiraterone Acetate

Other Name: ZYTIGA

Eligibility

Criteria:

Inclusion Criteria:

- Women aged ≥18 years;

- Histologically confirmed locally advanced or metastatic breast cancer;

- Triple negative breast cancer:

Estrogen receptor (ER)-negative and Progesterone 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*;

- 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);

- Patients could be chemotherapy naïve (provided they are not presenting with life-threatening metastasis) or have received any number of previous lines of chemotherapy (providing their life expectancy is ≥3 months);

- Pre and post menopausal patients are eligible.

- Measurable or non measurable disease according to RECIST v1.1 criteria;

- PS (ECOG) ≤2;

- Normal haematological function: ANC ≥1,500/mm3; platelets count ≥100,000/mm3; haemoglobin >10 g/dl;

- 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);

- Creatinine clearance (MDRD formula) ≥50 mL/min OR creatinine ≤1.5 times ULN;

- Normal kalemia (serum potassium ≥3.5 mM), natremia and magnesemia;

- 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);

- Cardiac ejection fraction ≥50% measured by MUGA or ECHO done within 4 weeks before inclusion;

- If receiving a bisphosphonate or denosumab, dose must have been stable for at least 2 doses before inclusion;

- Patient agreeing to use effective contraception during and for ≥ 6 months after completion of study treatment;

- Patient able to comply with the protocol;

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

- Patient must be affiliated to a Social Health Insurance.

Exclusion Criteria:

- Male breast cancer;

- 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;

- 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;

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

- Significant cardiovascular disease, including any of the following:

1. NYHA class III-IV congestive heart failure;

2. Unstable angina pectoris or myocardial infarction within the past 6 months;

3. Severe valvular heart disease;

4. Ventricular arrhythmia requiring treatment.

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

- Patients with known allergies, hypersensitivity or intolerance to abiraterone acetate, prednisone, or their excipients;

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

- Active or uncontrolled autoimmune disease requiring concurrent corticosteroid therapy;

- Any gastrointestinal disorder interfering with absorption of the study drug;

- Difficulties with swallowing study capsules;

- 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;

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

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

- 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;

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

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

Gender: Female

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Hervé BONNEFOI, Prof. Principal Investigator Institut Bergonié, Bordeaux
Location
Facility:
Ico - Site Paul Papin | Angers, France
Institut Sainte Catherine | Avignon, France
Chu - Hopital Jean Minjoz | Besancon, France
Institut Bergonie | Bordeaux, France
Polyclinique Bordeaux Nord Aquitaine | Bordeaux, France
Chu de Brest - Hôpital Morvan | Brest, France
Centre Francois Baclesse | Caen, France
Centre Jean Perrin | Clermont-ferrand, France
Ch Alpes Leman | Contamine - Sur - Arve, France
Centre Georges-François Leclerc | Dijon, France
Chu de Grenoble - Hopital Michallon | Grenoble, France
Clinique Sainte Marguerite | Hyeres, France
Chd de Vendee | La Roche-sur-yon, France
Centre Oscar Lambret | Lille, France
Centre Leon Berard | Lyon, France
Institut Paoli Calmettes | Marseille, France
Ch de Mont de Marsan | Mont de Marsan, France
Centre Antoine Lacassagne | Nice, France
Chr D Orleans - Hopital La Source | Orleans, France
Hôpital Saint-Louis | Paris, France
Hôpital Tenon | Paris, France
Institut Curie - Hôpital Claudius Regaud | Paris, France
Ch de Perpignan | Perpignan, France
Ch Lyon Sud | Pierre Benite, France
CH de la Région d'Annecy | Pringy, France
Institut Jean Godinot | Reims, France
Centre Henri Becquerel | Rouen, France
Institut Curie - Hôpital René Huguenin | Saint-cloud, France
Ico- Site Rene Gauducheau | Saint-herblain, France
Centre Paul Strauss | Strasbourg, France
Hopital Civil - Strasbourg | Strasbourg, France
Hopitaux Du Leman | Thonon Les Bains, France
Institut Claudius Regaud | Toulouse, France
Ch Bretagne Atlantique | Vannes, France
Hôpital Privé Océane | Vannes, France
Gustave Roussy Cancer Campus | Villejuif, France
Location Countries

France

Verification Date

February 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Abiraterone Acetate

Type: Experimental

Acronym AMA
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov