Clinical trial NCT01393730: Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: prostate
metastatic
castrate resistant
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2011-07-13
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Androgen Receptor (AR) Related Mutations
timeFrame: 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 outcomes:
measure: Change in Serum Levels of Testosterone
timeFrame: 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.
measure: Prostate-Specific Antigen (PSA) Response
timeFrame: 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.
measure: Time to PSA Progression
timeFrame: 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.
measure: Best Overall Response
timeFrame: 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.
measure: Time to Progression (TTP)
timeFrame: 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.
measure: Presence of AR Amplification
timeFrame: 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.
measure: Change in Serum Androgen Levels
timeFrame: 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.
measure: Change in Circulating Tumor Cells (CTCs) Levels
timeFrame: 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.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Mary-Ellen Taplin, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2014 Dec;17(4):325-31. doi: 10.1038/pcan.2014.28. Epub 2014 Aug 5.
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 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.
citation: 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.
citation: 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.