A Multicenter Phase I/II Trial of Abiraterone Acetate + BEZ235 in Metastatic, Castration-Resistant Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT01717898|
Recruitment Status : Terminated (Dose limiting toxicities on lowest dose level)
First Posted : October 31, 2012
Results First Posted : March 27, 2018
Last Update Posted : March 27, 2018
There will be two parts to this clinical research study. The purpose of each part is:
- Phase 1: This part of the study will determine what dose of BEZ235 is safe to give with a standard dose of abiraterone acetate and prednisone by administering different doses of BEZ235. This will help to find out what effects, good and/or bad, this combination has on CRPC.
- Phase 2: This part of the study will measure the treatment effect of the combination of BEZ235 and abiraterone acetate/prednisone on CRPC.
|Condition or disease||Intervention/treatment||Phase|
|Castrate-resistant Prostate Cancer||Drug: BEZ235 Drug: Prednisone Drug: Abiraterone acetate||Phase 1 Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Phase I/II Trial of Abiraterone Acetate + BEZ235 in Metastatic, Castration-Resistant Prostate Cancer|
|Actual Study Start Date :||January 31, 2013|
|Actual Primary Completion Date :||September 3, 2013|
|Actual Study Completion Date :||August 29, 2016|
Experimental: Abiraterone/prednisone + BEZ235
In Phase I, a dose escalation of BEZ235 will be performed using a standard 3 + 3 design to determine the maximum tolerated dose (MTD) of BEZ235 given in combination with continuous fixed doses of Abiraterone Acetate and prednisone. This BEZ235 dose will be used in the phase II portion of the study.
BEZ235 - 200 mg, 300 mg, or 400 mg; po, BID. BEZ235 will be supplied in 200 mg, 300 mg, and 400 mg sachets packaged in boxes.
10/mg po daily. Prednisone can be modified at the investigator's discretion, but should not be discontinued.
Drug: Abiraterone acetate
1000 mg, po. Abiraterone Acetate is supplied in 250 mg white tablets, four tablets are to be taken with a full glass of water on an empty stomach once daily.
Other Name: CB7630
- Number of Reported Dose Limiting Toxicities When Combining BEZ235 With Abiraterone Acetate (Phase I). [ Time Frame: Beginning of study up to 15 months ]
- Anti-tumor Responses as Defined by a Decline in PSA of > 50% [ Time Frame: From day 1 of therapy initiation up to 12 weeks ]Anti-tumor responses as defined by a decline in PSA of > 50% following 12 weeks of therapy to the combination of Abiraterone Acetate plus BEZ-235 occur in a cohort of patients who have received prior therapy with Abiraterone Acetate therapy
- Response Proportion as Defined by a Decline in PSA of > 50% [ Time Frame: From day 1 of therapy initiation up to 12 weeks ]
Response proportion as defined by a decline in PSA of > 50% following 12 weeks of therapy for patients treated with the combination of BEZ235 and Abiraterone Acetate plus Prednisone (Phase II outcome measure).
Study was terminated during Phase I, Dose level 1 due to toxicity, therefore no Phase II data is available.
- Maximum Tolerated Dose for BEZ235 + Abiraterone Acetate (Phase I). [ Time Frame: Beginning of study up to 15 months ]Maximum Tolerated Dose (MTD) for BEZ235 + Abiraterone Acetate (to be determined during Phase I). The MTD of BEZ235 will be the dose when given in combination results in less than 33% dose limiting toxicities (DLT).
- Trough Concentrations of BEZ235 and Abiraterone Acetate Plus Prednisone When Used in Combination [ Time Frame: Beginning of study up to 15 months ]Trough concentrations of BEZ235 and Abiraterone Acetate plus Prednisone when used in combination during Phase I.
- Progression Free Survival (PFS) in Phase II [ Time Frame: Beginning of Phase II up to 15 months ]Progression Free Survival (PFS) of the combination of BEZ235 plus Abiraterone Acetate/prednisone as determined by Prostate-Specific Antigen Working Group 2 criteria (PSAWG2 ) during Phase II.
- Determination of the Time to PSA Progression in Phase II [ Time Frame: Beginning of Phase II up to 15 months ]Determination of the time to PSA progression in Phase II based on PSAWG2 criteria.
- Objective Response Rate (ORR) in Phase II [ Time Frame: From beginning of Phase II up to 15 months ]Proportion of patients achieving an objective response to BEZ235 + Abiraterone Acetate/prednisone according to RECIST criteria.
- Safety of BEZ235 and Abiraterone Acetate Plus Prednisone When Used in Combination [ Time Frame: Beginning of Phase II up to 15 months ]Number of reported Adverse Events in BEZ235 and Abiraterone Acetate plus Prednisone when used in combination (Phase II).
- Determination of Whether the Pre-treatment Status of pS6, pAKT, p4EBP1 and PTEN, Determined by IHC in the Optional Biopsies of Metastatic Tumors, Are Associated With Response to BEZ235 Plus Abiraterone Acetate/Prednisone. [ Time Frame: post study ]
- Determination of Whether Specific Pathway Changes Are Predictive of Clinical Benefit (Improved PFS) or Resistance Prior to Treatment or During Treatment Using Microarray Analysis. [ Time Frame: post study ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01717898
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94115|
|Study Chair:||Charles Ryan, MD||University of California, San Francisco|