SWITCH: Study of the Prednisone to Dexamethasone Change in mCRPC Patients Treated With Abiraterone
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|ClinicalTrials.gov Identifier: NCT02928432|
Recruitment Status : Completed
First Posted : October 10, 2016
Last Update Posted : January 27, 2017
Abiraterone acetate (AA) has shown a favourable impact in overall survival, administered with prednisone to decrease the adverse event related to CYP171A suppression.
Our hypothesis is that the change of prednisone to dexamethasone in CRPC patients that progress biochemically to AA + prednisone can improve the number and the length of the responses, and also improve tolerance to treatment, decreasing the adverse events associated to a moderate dosage of steroids used chronically.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Steroids switch||Phase 2|
This phase II multicentric-study analyse the role of the steroid switch in patients receiving AA. Previous retrospective data (Lorente et al, BJC 2014) has shown that the change of prednisone by dexamethasone in CRPC patients treated with AA post-docetaxel leaded to durable biochemical responses in 40% of cases. Recently, superiority of dexamethasone over prednisone in PSA response has been reported by a phase II trial that included 82 chemotherapy-naive metastatic CRPC patients.
In our study patients with biochemical and/or limited radiological progression to AA + prednisone are prospectively enrolled. The principal objective was to evaluate the percentage of PSA responses in clinically stable metastatic CRPC patients after at least 12 weeks of AA + prednisone. Secondary aims will include time to biochemical progression, time to first radiological progression, overall survival and the evaluation of the safety profile.
Biochemical response was monitored with PSA determinations every 4 weeks, and defined as a ≥ 30% decline in PSA from baseline, confirmed with a second reading. PSA progression was evaluated according to PCWG2 criteria. Radiological response was re-evaluated every 12-16 weeks using bone and CT-scan according to RECIST v1.1 and PCWG2 criteria.
Translational studies: archival tissue will be obtained from all patients, to perform PTEN and TMPRSS-ERG rearrangements evaluation. Plasma will be collected after AA + prednisone progression to study the androgen receptor status in plasma.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||One-arm prospective|
|Masking:||None (Open Label)|
|Official Title:||Phase II Pilot Study of the Prednisone to Dexamethasone Switch in Metastatic Castration Resistant Prostate Cancer (CRPC) Patients With Asymptomatic Biochemical and/or Limited Radiological Progression on Abiraterone and Prednisone|
|Study Start Date :||June 2013|
|Actual Primary Completion Date :||September 2016|
|Actual Study Completion Date :||January 2017|
Experimental: Steroids switch
CRPC patients with biochemical and/or limited radiological progression after at least 12 weeks of AA + prednisone.
Drug: Steroids switch
Change of prednisone 5mg/12h to dexamethasone 0.5mg/24h
- To evaluate the percentage of PSA response in metastatic CRPC treated with AA + dexamethasone with biochemical and/or limited radiological progression. [ Time Frame: 12 months ]Biochemical response will be defined as a ≥ 30% decline in PSA from starting AA + dexamethasone, confirmed with a second PSA reading at least 2 weeks apart.
- To study time to biochemical (PSA) progression (>25% increase over PSA nadir value)in metastatic CRPC treated with AA + dexamethasone with biochemical and/or limited radiological progression. [ Time Frame: 12 months ]Time to biochemical progression is defined as the time from AA + dexamethasone starting data, to PSA progression according to PCWG2 criteria
- To analyze the time to radiological progression in metastatic CRPC treated with AA + dexamethasone with biochemical and/or limited radiological progression. [ Time Frame: 24 months ]Time to radiological progression is defined as the time from AA+ dexamethasone starting date to the first occurrence of either progression by bone scan or progression by CT-scan (based on RECIST v1.1 and PCWG2 criteria), or death resulting from any cause.
- To evaluate the overall survival in metastatic CRPC treated with AA + dexamethasone with biochemical and/or limited radiological progression. [ Time Frame: 24 months ]Overall survival is defined as the time from AA + dexamethasone starting date to the death or last follow up visit.
- To report the safety profile in in metastatic CRPC treated with AA + dexamethasone with biochemical and/or limited radiological progression. [ Time Frame: 24 months ]Toxicity events will be collected prospectively in each visit according to CTCAE v4.0 criteria.
- To describe the activity of subsequent treatment-line after AA + dexamethasone in the study population. [ Time Frame: 24 months ]Subsequent therapies and their corresponding biochemical/radiological responses will be also recorded.
- To explore potential androgen receptor pathway related circulating- and tissue-biomarkers in in metastatic CRPC treated with AA + dexamethasone with biochemical and/or limited radiological progression. [ Time Frame: 24 months ]Archival tissue for immunohistochemistry and FISH, and peripheral blood to extract plasma and perform AR amplification studies by ddPCR analysis and determination of AR Alternative splicing transcripts from exosomes.
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): NCT02928432
|Spanish National Cancer Research Centre (CNIO)|
|Madrid, Spain, 28029|