The Role of Androgen Deprivation Treatment (ADT) in Docetaxe-Prednisolone Chemotherapy for Castrate-Resistant Prostatic Cancer
The purpose of this study is to assess the androgen deprivation therapy when patients with castration-resistant prostate cancer are treated with docetaxel-based chemotherapy.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Phase II Screening Trial of Docetaxel Plus Prednisolone With or Without Androgen Deprivation Treatment in Castrate-Resistant Prostatic Cancer|
- Time to PSA progression [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Composite progression-free survival (PFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]PFS based on PSA, RECIST, bone scan, and performance status
- Overall survival [ Time Frame: 2 year ] [ Designated as safety issue: No ]
- PSA decline [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- PSA response to ADT retrial [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
ADT will be rechallenged to patients assigned to no ADT arm when their disease progress despite of docetaxel-prednisolone chemotherapy.
The PSA response to ADT rechallenge, such as PSA response based on PCWG v1.0, will be assessed and the number of patients with PSA response and the amount of PSA decline will be reported.
|Study Start Date:||July 2010|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: ADT arm
Concomitant androgen deprivation treatment
Luprolide 11.25 mg long-acting depo (Lucrin Depot PDS inj®) every 12 weeks SC wit Docetaxel-prednisolone (TAX327 regimen)
Active Comparator: No ADT arm
No concomitant androgen deprivation treatment arm
Drug: No ADT
Docetaxel-prednisolone (TAX327 regimen) alone
Androgen deprivation therapy (ADT) has been the mainstay in the treatment of metastatic prostate carcinoma. Despite initial favorable responses, predictable and irreversible resistance to ADT will occur in the vast majority of patients, which is defined as Castrate-Resistant prostate cancer (CRPC).
Recently, TAX327 study revealed docetaxel plus prednisolone could not only improve the QOL and PSA response but also prolong the survival in CRPC. It has been reasoned that discontinuation of ADT in nonorchiectomized patients may have detrimental effect on patients with CRPC as discontinuation of ADT can result in renewed release of testosterone and possible stimulation of remaining androgen-sensitive elements. When exogenous testosterone therapy is administered to patients with symptomatic CRPC, adverse responses can be induced. However, the lowest concentration of endogenous androgens that is capable of stimulating tumor growth is unknown. Data from animal models of androgen-dependent tumors showed that androgen-independent status is usually followed by androgen-insensitivity, which support the no need for ADT in CRPC. Contradictory, Dunning rat prostate cancer model cell lines, which are androgen-insensitive in vitro and grow slowly in the castrate rat, can grow more rapidly in a host with intact testis. In the retrospective observational study of CRPC treated with anthracycline, platinum, or ketoconazole, Taylor, et al. showed a modest, but statistically significant, survival advantage when ADT is continued. But, Hussain et al. and our team reported that there was no obvious advantage of continued ADT in response to cytotoxic chemotherapy or survival for in patients with CRPC. In addition, prospective trial conducted by Shamash, et al. showed that hormonal sensitivity can be reintroduced by stopping ADT during chemotherapy for CRPC. Among 43 patients who restarted androgen blockade after the completion of chemotherapy without ADT, 37% of patients had PSA response which was associated with survival advantage. Despite the limited and retrospective information available on the impact of continued ADT on disease outcome in CRPC when treated with cytotoxic chemotherapy, especially docetaxel containing regimen, ADT is frequently advocated to be used continuously. Considering little information on the benefit of continued ADT, and cost and side effects of ADT, prospective comparative studies are eagerly needed.
|Contact: Jae-Lyun Lee, MD, PhD||82 2 3010 email@example.com|
|Korea, Republic of|
|Asan Medical Center||Recruiting|
|Seoul, Korea, Republic of, 138-736|
|Contact: Hee Jeong Jeon, BSc|
|Contact: Jae-Lyun Lee, MD, PhD.|
|Sub-Investigator: Hanjong Ahn, MD, PhD.|
|Sub-Investigator: Jun-Hyuk Hong, MD, PhD.|
|Sub-Investigator: Cheryn Song, MD, PhD.|
|Sub-Investigator: In-Gab Jeong, MD, PhD|