Alisertib, Abiraterone Acetate and Prednisone in Treating Patients With Hormone-Resistant Prostate Cancer
Adenocarcinoma of the Prostate
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Drug: Abiraterone acetate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Alisertib in Combination With Abiraterone and Prednisone for Patients With Castration-Resistant Prostate Cancer After Progression on Abiraterone|
- Phase I: Frequency of dose limiting toxicities of Alisertib, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.1 [ Time Frame: Up to 21 days ] [ Designated as safety issue: Yes ]Summarized with descriptive statistics.
- Phase II: Duration of progression free survival according to the PCWG2 criteria [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]The Kaplan-Meier product limit method will be used to estimate the probability distribution of progression free survival (PFS). The proportion of patients achieving at least a 50% decline from baseline will be reported with a 95% confidence interval. The results will be presented graphically using a waterfall plot.
- Change in PSA kinetics [ Time Frame: Baseline up to 3 months ] [ Designated as safety issue: No ]Compared between the two patient subsets using the nonparametric Mann-Whitney test. A comparison of CTC counts between baseline and at progression for those who have progressed will be carried out using either a paired t test or the nonparameteric Wilcoxon matched pairs test.
|Study Start Date:||August 2013|
|Estimated Primary Completion Date:||May 2018 (Final data collection date for primary outcome measure)|
Experimental: Treatment (alisertib, abiraterone acetate, prednisone)
Patients receive alisertib PO BID on days 1-7, abiraterone acetate PO daily, and prednisone PO BID. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other Name: MLN8237Drug: Abiraterone acetate
Other Names:Drug: Prednisone
- Phase I: To determine the safe dose of alisertib when given in combination with abiraterone (abiraterone acetate) and prednisone in metastatic castration resistant prostate cancer (mCRPC) patients with disease progression on abiraterone and prednisone.
- Phase II: To determine the proportion of patients who have no disease progression after alisertib is added to abiraterone and prednisone.
- Phase II: To determine the prostate specific antigen (PSA) kinetics after alisertib is added to abiraterone and prednisone regimen (this includes the proportion of patients with PSA progression free at 3 months, proportion of patients with 50% PSA reduction after study treatment, maximum PSA decline from baseline during the first 12 weeks).
- Phase II: To compare baseline circulating tumor cells (CTCs) enumeration to 12 week post-therapy CTC enumeration.
- Phase II: To compare baseline neuroendocrine marker (chromogranin A and neuron-specific enolase [NSE]) levels to 12 week post therapy neuroendocrine marker levels.
- Phase II: To further assess overall safety of combination of alisertib with abiraterone and prednisone in the phase 1 portion of the study.
OUTLINE: This is a phase I, dose escalation study of alisertib followed by a phase II study.
Patients receive alisertib orally (PO) twice daily (BID) on days 1-7, abiraterone acetate PO daily, and prednisone PO BID. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01848067
|United States, Pennsylvania|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||Jianqing Lin, MD||Thomas Jefferson University|