The Role of Androgen Deprivation Treatment (ADT) in Docetaxe-Prednisolone Chemotherapy for Castrate-Resistant Prostatic Cancer

Castration-resistant Prostate Cancer Clinical Trial

Official title:

Randomized Phase II Screening Trial of Docetaxel Plus Prednisolone With or Without Androgen Deprivation Treatment in Castrate-Resistant Prostatic Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01487902
• Other study ID #: UOSG-AMC-0803
• Status: Recruiting
• Phase: Phase 2
• First received: December 5, 2011
• Last updated: December 7, 2011
• Start date: July 2010

Study information

• Verified date: December 2011
• Source: Asan Medical Center
• Contact: Jae-Lyun Lee, MD, PhD
• Phone: 82 2 3010 5977
• Email: jaelyun[@]amc.seoul.kr
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate

• Clinical or radiologic evidence of metastatic disease

• Documented disease progression during hormone therapy (ADT with or without antiandrogen)

• Cessation of ADT at least 4 weeks in non-orchiectomized patients

• Adequate duration (at least 4 weeks for flutamide and 6 weeks for bicalutamide) of anti-androgen withdrawal (only for patients who showed a response or decline in PSA for more than 3 months)

• KPS = 60

• No prior cyto-toxic chemotherapy (except estramustine) or radioisotopes

• No prior radiotherapy 25% or more of the bone marrow

• No peripheral neuropathy grade 2 or worse

• Adequate organ and bone marrow function

Exclusion Criteria:

• Other tumor type than adenocarcinoma

• Presence or history of CNS metastasis

• Other serious illness or medical conditions

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• ADT
Luprolide 11.25 mg long-acting depo (Lucrin Depot PDS inj®) every 12 weeks SC wit Docetaxel-prednisolone (TAX327 regimen)
• No ADT
Docetaxel-prednisolone (TAX327 regimen) alone

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to PSA progression		1 year	No
Secondary	Composite progression-free survival (PFS)	PFS based on PSA, RECIST, bone scan, and performance status	1 year	No
Secondary	Overall survival		2 year	No
Secondary	PSA decline		12 weeks	No
Secondary	PSA response to ADT retrial	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.	12 weeks	No

External Links

•   Retrospective study on the role of ADT