Clinical trial NCT01842321: Abiraterone Acetate in Molecular Apocrine Breast Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: locally advanced
metastatic
Breast Cancer
Molecular Apocrine
HER2-negative
Abiraterone acetate
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2013-04-29
Enrollment: 34
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical benefit rate (CBR)
timeFrame: at 6 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: at 6 months
measure: Duration of overall response (DoR)
timeFrame: at 6 months
measure: Overall Survival (OS)
timeFrame: median follow-up = 2 years
measure: Progression-free survival (PFS)
timeFrame: median follow-up = 2 years
measure: Overall safety profile
timeFrame: 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)
Other outcomes:
Locations:
city: Angers
country: France
facility: Ico - Site Paul Papin
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Besancon
country: France
facility: Chu - Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Brest
country: France
facility: Chu de Brest - Hôpital Morvan
city: Caen
country: France
facility: Centre Francois Baclesse
city: Clermont-ferrand
country: France
facility: Centre Jean Perrin
city: Contamine - Sur - Arve
country: France
facility: Ch Alpes Leman
city: Dijon
country: France
facility: Centre Georges-François Leclerc
city: Grenoble
country: France
facility: Chu de Grenoble - Hopital Michallon
city: Hyeres
country: France
facility: Clinique Sainte Marguerite
city: La Roche-sur-yon
country: France
facility: Chd de Vendee
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Mont de Marsan
country: France
facility: Ch de Mont de Marsan
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orleans
country: France
facility: Chr D Orleans - Hopital La Source
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Tenon
city: Paris
country: France
facility: Institut Curie - Hôpital Claudius Regaud
city: Perpignan
country: France
facility: Ch de Perpignan
city: Pierre Benite
country: France
facility: Ch Lyon Sud
city: Pringy
country: France
facility: CH de la Région d'Annecy
city: Reims
country: France
facility: Institut Jean Godinot
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-cloud
country: France
facility: Institut Curie - Hôpital René Huguenin
city: Saint-herblain
country: France
facility: Ico- Site Rene Gauducheau
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: Hopital Civil - Strasbourg
city: Thonon Les Bains
country: France
facility: Hopitaux Du Leman
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Vannes
country: France
facility: Ch Bretagne Atlantique
city: Vannes
country: France
facility: Hôpital Privé Océane
city: Villejuif
country: France
facility: Gustave Roussy Cancer Campus
Study officials:
affiliation: Institut Bergonié Bordeaux
name: Hervé BONNEFOI, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bonnefoi H, Grellety T, Tredan O, Saghatchian M, Dalenc F, Mailliez A, L'Haridon T, Cottu P, Abadie-Lacourtoisie S, You B, Mousseau M, Dauba J, Del Piano F, Desmoulins I, Coussy F, Madranges N, Grenier J, Bidard FC, Proudhon C, MacGrogan G, Orsini C, Pulido M, Goncalves A. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol. 2016 May;27(5):812-8. doi: 10.1093/annonc/mdw067. Epub 2016 Feb 18.