Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01393730
First received: June 21, 2011
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

The purpose of this research study is to determine if the addition of dutasteride to a regimen with abiraterone acetate and prednisone will improve on therapy in patients with castrate-resistant prostate cancer and metastatic disease. This study will also help determine the side effects of the study treatment and how often they occur.


Condition Intervention Phase
Prostate Cancer
Drug: Abiraterone acetate
Drug: Dutasteride
Drug: Prednisone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Abiraterone Acetate Combined With Dutasteride With Correlative Assessment of Tumor Androgen Levels and Androgen Receptor Sequence and Signaling at Baseline and at Progression

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To analyze possible AR related mechanisms of abiraterone acetate resistance in serial CRPC metastasis biopsies. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To analyze possible AR related mechanisms of abiraterone acetate resistance in serial CRPC metastasis biopsies (including AR sequence-mutations/splice variants, AR regulated gene expression, tumor androgen levels and profiling enzymes involved in androgen synthesis and metabolism).


Secondary Outcome Measures:
  • Assessment of serum levels of testosterone, dihydrotestosterone and androgen precursors at baseline and at progression. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess serum levels of testosterone, dihydrotestosterone and androgen precursors at baseline and at progression on combined Abiraterone acetate-prednisone/Dutasteride.

  • Assessment of PSA response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess PSA response to Abiraterone acetate-prednisone at 2 months and on combined Abiraterone acetate-prednisone/Dutasteride. PSA decline will be measured according to PSAWG-2 (2008) criteria. PSA changes will be recorded on all patients. Time to PSA progression (TTP) will be based on revised PSA Working Group-2 criteria.

  • Assessment of PSA response duration on Abiraterone acetate-prednisone/Dutasteride [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess PSA response duration on Abiraterone acetate-prednisone/Dutasteride. PSA decline will be measured according to PSAWG-2 (2008) criteria. PSA changes will be recorded on all patients. Time to PSA progression (TTP) will be based on revised PSA Working Group-2 criteria

  • To assess response of measurable disease if present [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria.

  • To assess time to progression of bone lesions or measurable disease (RECIST) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessment of time to progression of bone lesions or measurable disease using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

  • Assessment of toxicity of Abiraterone acetate and Dutasteride [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Number of participants with Adverse Events as a measure to assess toxicity of Abiraterone acetate and Dutasteride

  • To correlate presence of AR amplification [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To correlate presence of AR amplification, AR mutatiion, AR splice variants, TMPRSS2/ERG, AR regulated gene expression, tumor androgens, serum androgens with PSA and radiographic response to Abiraterone acetate-prednisone/Dutasteride

  • To measure serum androgens and CTCs [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To measure serum androgens and circulating tumor cells (CTCs) as a marker of response to Abiraterone acetate-prednisone and Abiraterone acetate-prednisone/Dutasteride

  • Evaluation of methods for using CTCs for RNA based expression profiling of AR and AR regulated genes as an exploratory endpoint. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Circulating tumor cells (CTC's) will be assessed. The association between the number of CTCs and response will be described, although statistical power will be limited. Exploratory analyses of the associations between CTCs and parameters associated with AR activity will be done.


Estimated Enrollment: 33
Study Start Date: September 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Abiraterone acetate
    1000 mg orally, once per day
    Other Name: CB7630
    Drug: Dutasteride
    3.5 mg orally once per day
    Other Name: Avodart
    Drug: Prednisone
    5 mg orally once per day
Detailed Description:

Patients will receive abiraterone acetate and prednisone orally, once daily for 2 months (2 cycles) on an outpatient basis. At the start of cycle 3, dutasteride will be taken once daily. Patients will return to the clinic on Day 14 of the first 3 cycles for routine blood tests.

Patients will come to the clinic every 12 weeks for a CT scan and/or x-ray of the chest, CT scan or MRI of the abdomen and pelvis, bone scan, and blood test for testosterone and other specialized blood test.

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of adenocarcinoma of the prostate
  • Castrate resistant disease
  • Metastatic disease
  • Normal organ and marrow function
  • Subjects with partners of childbearing potential must be willing to use adequate methods of birth control

Exclusion Criteria:

  • Uncontrolled intercurrent illness
  • Uncontrolled hypertension
  • Active or symptomatic viral hepatitis or chronic liver disease
  • History of pituitary or adrenal dysfunction
  • Clinically significant heart disease
  • History of a different malignancy unless disease-free for at least 5 years
  • Known brain metastasis
  • History of gastrointestinal disorders
  • Prior therapy with abiraterone acetate
  • HIV-positive individuals on antiretroviral therapy
  • Requirement for steroid use greater than the equivalent of 5 mg of prednisone daily
  • Atrial fibrillation or other cardiac arrhythmia requiring therapy
  • Thromboembolism in the last 6 months
  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: NCT01393730

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Mary-Ellen Taplin, MD
Investigators
Principal Investigator: Mary-Ellen Taplin, M.D. Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Mary-Ellen Taplin, MD, Associate Professor of Medicine, HMS, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01393730     History of Changes
Other Study ID Numbers: 10-448
Study First Received: June 21, 2011
Last Updated: January 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
prostate
metastatic
castrate resistant

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Dutasteride
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents
5-alpha Reductase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014