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

NCT ID: NCT01487902

Last Updated: 2011-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Castration-resistant Prostate Cancer

Keywords

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Chemotherapy-naive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ADT arm

Concomitant androgen deprivation treatment

Group Type EXPERIMENTAL

ADT

Intervention Type DRUG

Luprolide 11.25 mg long-acting depo (Lucrin Depot PDS inj®) every 12 weeks SC wit Docetaxel-prednisolone (TAX327 regimen)

No ADT arm

No concomitant androgen deprivation treatment arm

Group Type ACTIVE_COMPARATOR

No ADT

Intervention Type DRUG

Docetaxel-prednisolone (TAX327 regimen) alone

Interventions

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ADT

Luprolide 11.25 mg long-acting depo (Lucrin Depot PDS inj®) every 12 weeks SC wit Docetaxel-prednisolone (TAX327 regimen)

Intervention Type DRUG

No ADT

Docetaxel-prednisolone (TAX327 regimen) alone

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Asan Medical Center

OTHER

Sponsor Role lead

Responsible Party

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JLee

Associate professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Jae-Lyun Lee, MD, PhD

Role: CONTACT

Phone: 82 2 3010 5977

Email: [email protected]

Facility Contacts

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Hee Jeong Jeon, BSc

Role: primary

Jae-Lyun Lee, MD, PhD.

Role: backup

Related Links

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http://www.ncbi.nlm.nih.gov/pubmed/20686407

Retrospective study on the role of ADT

Other Identifiers

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UOSG-AMC-0803

Identifier Type: -

Identifier Source: org_study_id