Abiraterone Acetate in Treating Postmenopausal Women With Advanced or Metastatic Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Cancer Research UK
Sponsor:
Information provided by (Responsible Party):
Cancer Research UK
ClinicalTrials.gov Identifier:
NCT00755885
First received: September 18, 2008
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

RATIONALE: Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of abiraterone acetate and to see how well it works in treating postmenopausal women with advanced or metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: abiraterone acetate
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Cancer Research UK Phase I/II Open Label Study to Evaluate the Safety, Endocrine Effects and Anti-tumour Activity of Abiraterone Acetate (CB7630) in Patients With Oestrogen (ER) or Androgen Receptor (AR) Positive Advanced or Metastatic Breast Carcinoma

Resource links provided by NLM:


Further study details as provided by Cancer Research UK:

Primary Outcome Measures:
  • Causality of each adverse event and grading severity as measured by NCI CTCAE v3.0 (Phase I) [ Designated as safety issue: Yes ]
  • Maximum tolerated dose (MTD) of abiraterone acetate (Phase I) [ Designated as safety issue: Yes ]
  • Proportion of patients with stable disease for ≥ 24 weeks or objective response as measured by RECIST criteria (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma levels of abiraterone acetate as measured by liquid chromatography/tandem mass spectrometry assay (Phase I) [ Designated as safety issue: No ]
  • Relationship between dose and endocrine response (Phase I) [ Designated as safety issue: No ]
  • Duration of objective tumor response as measured by RECIST criteria (Phase II) [ Designated as safety issue: No ]
  • Relationship between tumor response and endocrine response (Phase II) [ Designated as safety issue: No ]
  • Median overall survival (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: October 2008
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the safety and tolerability of abiraterone acetate in postmenopausal women with estrogen receptor- or androgen receptor-positive advanced or metastatic breast cancer. (Phase I)
  • To determine the recommended phase II dose of this drug in these patients. (Phase I)
  • To evaluate the clinical benefit rate of this drug at 24 weeks in these patients. (Phase II)

Secondary

  • To study the pharmacokinetics of this drug in these patients. (Phase I)
  • To determine the endocrine impact of this drug on the pituitary-adrenal-gonad endocrine axis. (Phase I)
  • To estimate the duration of objective tumor response in these patients. (Phase II)
  • To correlate response rates and duration of response with the endocrine profile in these patients. (Phase II)
  • To determine overall survival of these patients. (Phase II)

Tertiary

  • To enumerate and molecularly characterize circulating tumor cells.
  • To identify normal genetic variations that predict resistance to this drug using pharmacogenomic analysis.

OUTLINE: This is a multicenter, phase I study followed by a phase II study. Patients enrolled in the phase II portion of the study are stratified according to hormone receptor status (estrogen receptor [ER]-positive and any androgen receptor [AR] status vs AR-positive and ER-negative).

Patients receive oral abiraterone acetate once daily on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically and analyzed for pharmacokinetic assays (phase I only), pharmacodynamic assays, circulating tumor cells, and pharmacogenomic analysis.

After completion of study treatment, patients are followed for 28 days.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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:

    1. Aged > 60 years or
    2. Aged 45-59 years with intact uterus and amenorrhoeic for at least 12 months or
    3. 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
    4. Aged > 18 years having had a bilateral surgical oophorectomy.
  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 Organization (WHO) performance status of 0-2 (Appendix 1).
  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) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (5 x ULN in the presence of liver metastases) Creatinine clearance

    Or:

    Creatinine ≥50 ml/min

    < 1.5 x ULN

  10. Normal potassium and magnesium levels.
  11. Normal baseline ACTH stimulation test
  12. Systolic blood pressure < 160 and diastolic < 95 mmHg documented on at least 3 different occasions. Hypertension currently under control is permitted.
  13. Cardiac Ejection Fraction > or = 50% measured by MUGA scan / ECHO
  14. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.

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 nitrosoureas 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/tablets.
  7. Clinical and/or biochemical evidence of hyperaldosteronism or hypopituitarism.
  8. History of thromboembolic 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:

    1. Congestive heart failure with severity NYHA III or IV (see Appendix 4);
    2. History of unstable angina pectoris or myocardial infarction up to 6 months prior to trial entry;
    3. Presence of severe valvular heart disease;
    4. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00755885

Locations
United Kingdom
Guy's Hospital Recruiting
London, England, United Kingdom, SE1 9RT
Contact: Contact Person    207-188-4237      
Royal Marsden - Surrey Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Contact Person    44-208-722-4028    Johann.De-Bono@icr.ac.uk   
University of Birmingham, Recruiting
Birmingham, United Kingdom, B15 2TT
Contact: Contact Person    0121 414 7611    d.w.rea@bham.ac.uk   
Western General Hospital Recruiting
Edinburgh, United Kingdom, EH4 2XU
Contact: Contact Person    0131 537 1042    Angela.Bowman@ed.ac.uk   
The Beatson West of Scotland Cancer Centre Recruiting
Glasgow, United Kingdom, G12 0YN
Contact: Contact Person    0141 301 7128    Iain.MacPherson@ggc.scot.nhs.uk   
Sponsors and Collaborators
Cancer Research UK
Investigators
Principal Investigator: Johann Sebastian de Bono, MD Cancer Research UK
  More Information

Additional Information:
No publications provided

Responsible Party: Cancer Research UK
ClinicalTrials.gov Identifier: NCT00755885     History of Changes
Other Study ID Numbers: CDR0000614059, CRUK-CR9304-21, EUDRACT-2007-003240-30
Study First Received: September 18, 2008
Last Updated: September 24, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Cancer Research UK:
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
recurrent breast cancer
estrogen receptor-positive breast cancer
progesterone receptor-positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014