Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer

• 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: Mary-Ellen Taplin, MD
• Information provided by (Responsible Party): Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Abiraterone acetate; Drug: Dutasteride; Drug: Prednisone	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: September 2011
• Actual Primary Completion Date: January 2016
• Actual Study Completion Date: March 15, 2017

Arms and Interventions

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	Drug: Abiraterone acetate; Other Name: CB7630; Drug: Dutasteride; Other Name: Avodart; Drug: Prednisone; Other Name: Corticosteroid

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes 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

Locations

United States, Massachusetts

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Washington

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

University of Washington Medical Center

Seattle, Washington, United States, 98195

Sponsors and Collaborators

Mary-Ellen Taplin, MD

Investigators

• Principal Investigator: Mary-Ellen Taplin, M.D.; Dana-Farber Cancer Institute

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Mary-Ellen Taplin, MD, Associate Professor of Medicine, HMS, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01393730
• Other Study ID Numbers: 10-448
• First Posted: July 13, 2011
• Results First Posted: June 14, 2017
• Last Update Posted: March 15, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: This will not be done.

Keywords provided by Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute:

prostate; metastatic; castrate resistant

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Prednisone; Abiraterone Acetate; Dutasteride; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; 5-alpha Reductase Inhibitors