Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01393730
• Other study ID #: 10-448
• Status: Completed
• Phase: Phase 2
• First received: June 21, 2011
• Last updated: February 16, 2018
• Start date: September 2011
• Est. completion date: March 15, 2017

Study information

• Verified date: February 2018
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 15, 2017
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Abiraterone acetate

• Dutasteride

• Prednisone

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Mary-Ellen Taplin, MD

Country where clinical trial is conducted

United States, 

References & Publications (3)

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 proges — View Citation

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 wit — View Citation

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-res — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Androgen Receptor (AR) Related Mutations	AR related mutation was defined as presence of T878A mutation. Expression of T878A was measured by established methods.	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.
Secondary	Change in Serum Levels of Testosterone	Serum testosterone levels were estimated based on established methods. The change from baseline to progression was calculated for each participant.	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.
Secondary	Prostate-Specific Antigen (PSA) Response	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.	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.
Secondary	Time to PSA Progression	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.	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.
Secondary	Best Overall Response	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.	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.
Secondary	Time to Progression (TTP)	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.	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.
Secondary	Presence of AR Amplification	Presence of AR amplification was measured by established methods.	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.
Secondary	Change in Serum Androgen Levels	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.
Secondary	Change in Circulating Tumor Cells (CTCs) Levels	CTCs were measured based on established methods.	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.