- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01393730
Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer
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
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
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Washington
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Seattle, Washington, United States, 98109
- Seattle Cancer Care Alliance
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Seattle, Washington, United States, 98195
- University of Washington Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
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Other Names:
Other Names:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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AR related mutation was defined as presence of T878A mutation.
Expression of T878A was measured by established methods.
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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.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Serum testosterone levels were estimated based on established methods.
The change from baseline to progression was calculated for each participant.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Presence of AR amplification was measured by established methods.
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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.
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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.
|
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.
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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.
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CTCs were measured based on established methods.
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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.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mary-Ellen Taplin, M.D., Dana-Farber Cancer Institute
Publications and helpful links
General Publications
- McKay RR, Zukotynski KA, Werner L, Voznesensky O, Wu JS, Smith SE, Jiang Z, Melnick K, Yuan X, Kantoff PW, Montgomery B, Balk SP, Taplin ME. Imaging, procedural and clinical variables associated with tumor yield on bone biopsy in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2014 Dec;17(4):325-31. doi: 10.1038/pcan.2014.28. Epub 2014 Aug 5.
- McKay RR, Werner L, Mostaghel EA, Lis R, Voznesensky O, Zhang Z, Marck BT, Matsumoto AM, Domachevsky L, Zukotynski KA, Bhasin M, Bubley GJ, Montgomery B, Kantoff PW, Balk SP, Taplin ME. A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2017 Feb 15;23(4):935-945. doi: 10.1158/1078-0432.CCR-16-0987. Epub 2016 Sep 28. Erratum In: Clin Cancer Res. 2017 Jul 15;23 (14 ):3970.
- Chen EJ, Sowalsky AG, Gao S, Cai C, Voznesensky O, Schaefer R, Loda M, True LD, Ye H, Troncoso P, Lis RL, Kantoff PW, Montgomery RB, Nelson PS, Bubley GJ, Balk SP, Taplin ME. Abiraterone treatment in castration-resistant prostate cancer selects for progesterone responsive mutant androgen receptors. Clin Cancer Res. 2015 Mar 15;21(6):1273-80. doi: 10.1158/1078-0432.CCR-14-1220. Epub 2014 Oct 15.
- Wang Z, Deng T, Long X, Lin X, Wu S, Wang H, Ge R, Zhang Z, Wu CL, Taplin ME, Olumi AF. Methylation of SRD5A2 promoter predicts a better outcome for castration-resistant prostate cancer patients undergoing androgen deprivation therapy. PLoS One. 2020 Mar 5;15(3):e0229754. doi: 10.1371/journal.pone.0229754. eCollection 2020.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Steroid Synthesis Inhibitors
- 5-alpha Reductase Inhibitors
- Prednisone
- Abiraterone Acetate
- Dutasteride
Other Study ID Numbers
- 10-448
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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