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Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT01393730
Recruitment Status : Completed
First Posted : July 13, 2011
Results First Posted : June 14, 2017
Last Update Posted : March 15, 2018
Sponsor:
Information provided by (Responsible Party):
Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE June 21, 2011
First Posted Date  ICMJE July 13, 2011
Results First Submitted Date  ICMJE March 17, 2017
Results First Posted Date  ICMJE June 14, 2017
Last Update Posted Date March 15, 2018
Study Start Date  ICMJE September 2011
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2017)
Number of Participants With Androgen Receptor (AR) Related Mutations [ Time Frame: Pairs of patients samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. ]
AR related mutation was defined as presence of T878A mutation. Expression of T878A was measured by established methods.
Original Primary Outcome Measures  ICMJE
 (submitted: July 12, 2011)
To analyze possible AR related mechanisms of abiraterone acetate resistance in serial CRPC metastasis biopsies. [ Time Frame: 2 years ]
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).
Change History Complete list of historical versions of study NCT01393730 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2017)
  • Change in Serum Levels of Testosterone [ Time Frame: Samples for testosterone analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. ]
    Serum testosterone levels were estimated based on established methods. The change from baseline to progression was calculated for each participant.
  • Prostate-Specific Antigen (PSA) Response [ Time Frame: PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. ]
    PSA response was defined as decline of 50% from baseline confirmed by a PSA at least 4 weeks later based on Prostate-specific Antigen Working Group-2 (PSAWG-2) (2008) criteria.
  • Time to PSA Progression [ Time Frame: PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. ]
    Time to PSA progression based on the Kaplan-Meier method was defined as the time between registration and documented PSA progression. PSA progression based on Prostate-Specific Antigen Working Group-2 (PSAWG-2) (2008) criteria was an increase of >/=25% and >/= 2 ng/ml after 12 weeks for patients without a PSA decline from baseline and an increase of >/=25% and >/= 2 ng/ml above the nadir, confirmed by a 2nd value 3 weeks or later for patients with a PSA decline from baseline. PSA progression was reported not duration of response.
  • Best Overall Response [ Time Frame: Disease was evaluated radiologically at baseline and every 12 weeks cycles on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. ]
    Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
  • Time to Progression (TTP) [ Time Frame: Disease evaluation occurred every 12 weeks while patients were receiving treatment. In this study cohort, participants were followed up to 48 months for this endpoint. ]
    TTP based on the Kaplan-Meier method is defined as the duration of time from study entry to documented first observation of progressive disease (PD). Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
  • Presence of AR Amplification [ Time Frame: Patients' samples were evaluated at baseline and every 12 weeks on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. ]
    Presence of AR amplification was measured by established methods.
  • Change in Serum Androgen Levels [ Time Frame: Pairs of patients' samples for androgen analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. ]
    Serum androgen levels measured based on established methods. The change from baseline to progression was calculated for each participant.
  • Change in Circulating Tumor Cells (CTCs) Levels [ Time Frame: Pairs of patients' samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. ]
    CTCs were measured based on established methods.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2011)
  • Assessment of serum levels of testosterone, dihydrotestosterone and androgen precursors at baseline and at progression. [ Time Frame: 2 years ]
    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 ]
    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 ]
    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 ]
    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 [21]. 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 ]
    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 ]
    Number of participants with Adverse Events as a measure too assess toxicity of Abiraterone acetate and Dutasteride
  • To correlate presence of AR amplification [ Time Frame: 2 years ]
    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 ]
    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 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer
Official Title  ICMJE 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
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Abiraterone acetate
    Other Name: CB7630
  • Drug: Dutasteride
    Other Name: Avodart
  • Drug: Prednisone
    Other Name: Corticosteroid
Study Arms  ICMJE Experimental: Abiraterone+prednisone+dutasteride
Abiraterone acetate 1000mg orally once per day + prednisone 5mg orally once per day for two months, followed by abiraterone 1000mg orally once per day + prednisone 5mg orally once per day + dutasteride 3.5mg orally once per day in 28-day cycles until symptomatic or radiographic progression
Interventions:
  • Drug: Abiraterone acetate
  • Drug: Dutasteride
  • Drug: Prednisone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 12, 2017)
40
Original Estimated Enrollment  ICMJE
 (submitted: July 12, 2011)
33
Actual Study Completion Date  ICMJE March 15, 2017
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01393730
Other Study ID Numbers  ICMJE 10-448
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: This will not be done.
Responsible Party Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Mary-Ellen Taplin, MD
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mary-Ellen Taplin, M.D. Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP