Oestrogen (ER) or androgen receptor (AR) positive, advanced or metastatic breast carcinoma MedDRA version: 16.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Abiraterone Actetate
Product Code: CB7630
Pharmaceutical Form: Tablet
INN or Proposed INN: Abiraterone Acetate
Current Spo
Sponsors
Cancer Research UK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed advanced or metastatic breast carcinoma 2. Evidence of disease progression (off treatment) prior to trial commencement. 3. All patients must have received previous treatment in the adjuvant or metastatic setting: - ER+ patients must have received at least two types of hormone therapy (e.g. aromatase inhibitors and Tamoxifen) - HER2+ patients must have received Herceptin plus at least one other line of chemotherapy - HER - ER- patients must have received at least one line of chemotherapy 4. Post-menopausal defined by: a) Aged > 60 years or b) Aged > 45 years with intact uterus and amenorrhoeic for at least 12 months or c) Aged > 40 years (has not received chemotherapy in the past 12 months) and no menstrual periods for 12 consecutive months (no other biological/physiological cause identified) and hormone levels are consistent with post menopausal status or d) Aged > 18 years having had a bilateral surgical oopherectomy. 5. Either ER+ (any AR) or AR+ (ER-) disease (by immunohistochemistry) 6. For Phase II only: Measurable disease by RECIST criteria. 7. Life expectancy of at least 3 months. 8. World Health Organisation (WHO) performance status of 0-2. 9. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before the patient goes on study. Lab Test Value required - Haemoglobin (Hb) =9.0 g/dl - Neutrophils =1.5 x 10(9)/L - Platelets =100 x 10(9)/L - Total bilirubin =1.5 x upper normal limit (ULN) - ALT and AST = 2.5 x ULN (5 x ULN in the presence of liver metastases) - Creatinine clearance =50 ml/min Or: Creatinine = 1.5 x ULN 10. Normal potassium and magnesium levels 11. Normal baseline ACTH stimulation test (this will not be required in the Phase II study if no evidence of adrenal insufficiency is observed in the Phase I study). 12. Systolic blood pressure =65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. Anti-cancer therapy including radiotherapy (except for palliative reasons), any endocrine therapy, immunotherapy, chemotherapy, or use of other investigational agents within four weeks prior to trial entry (six weeks for nitrosureas and Mitomycin-C). 2. ER-and AR- breast cancer by immunohistochemistry 3. Persistent grade 2 or greater toxicities from any cause (Exceptions to this are alopecia or certain Grade 2 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient). 4. Patients with known Central Nervous System (CNS) disease (primary or secondary) or leptomeningeal disease because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events. 5. Gastrointestinal disorders interfering with absorption of the study drug 6. Difficulties with swallowing study capsules 7. Clinical and/or biochemical evidence of hyperaldosteronism or hypopituitarism 8. History of thrombo-embolic disease within 12 months of commencing this trial 9. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies 10. Major thoracic and/or abdominal surgery or significant traumatic injury within 4 weeks prior to trial entry from which the patient has not recovered 11. At high medical risk because of non-malignant systemic disease including active infection or serious concurrent illness 12. Active or uncontrolled autoimmune disease that may require corticosteroid therapy during protocol treatment 13. Known immunocompromised patients, e.g. Human Immunodeficiency Virus (HIV). 14. Current malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study. 15. Significant cardiovascular disease as defined by: a. Congestive heart failure with severity NYHA III or IV (see Appendix 4); b. History of unstable angina pectoris or myocardial infarction up to 6 months prior to trial entry; c. Presence of severe valvular heart disease; d. Presence of a ventricular arrhythmia requiring treatment. 16. Any other condition which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I 1. To evaluate the safety and tolerability of abiraterone acetate administered orally continuously in a once-daily regimen in post-menopausal women with advanced breast malignancy. 2. To recommend a trial dose for the Phase II. Phase II 1. To evaluate the clinical benefit rate in post-menopausal women with ER+ or AR+ER- advanced breast cancer at 24 weeks i.e 6 cycles ; Secondary Objective: Phase I 1. To study abiraterone acetate pharmacokinetics in post-menopausal women. 2. To determine the endocrine impact of abiraterone acetate on the pituitary-adrenal-gonad endocrine axis. 3. To document any anti-tumour activity Phase II 1. To estimate the duration of objective tumour responses in the two patient cohorts (according to intra-tumoural ER and AR expression). 2. To correlate response rates and duration of response with the endocrine profile (at baseline and brought about by abiraterone acetate). 3. To evaluate two year survival (post Cycle 1 Day 1), after treatment with CB7630 in the two cohorts. ; Primary end point(s): Phase I 1. Determining causality of each adverse event to abiraterone acetate and grading severity according to NCI CTCAE Version 3.0. 2. The Maximum Tolerated Dose (MTD) or 1000 mg (if MTD is not reached) Phase II 1. Determining the proportion of patients with stable disease for = 24 weeks or objective response according to RECIST criteria ;Timepoint(s) of evaluation of this end point: Throughout study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 24 weeks; Secondary end point(s): Phase I a) Plasma levels of abiraterone measured using a validated LC-MS-MS assay. b) Determining the relationship between dose and endocrine response (and determining the recommended dose for Phase II if MTD is not reached). c) Disease response as assessed by RECIST criteria Phase II a) Determining the duration of objective tumour responses according to RECIST criteria in each cohort. b) Determining the relationship between tumour and endocrine responses in each cohort. c) Determining two year survival in each cohort. | — |
Countries
United Kingdom
Contacts
Public ContactDrug Development Office
Cancer Research UK
Outcome results
None listed