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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01487902
Recruitment Status : Unknown
Verified December 2011 by JLee, Asan Medical Center.
Recruitment status was:  Recruiting
First Posted : December 8, 2011
Last Update Posted : December 8, 2011
Information provided by (Responsible Party):
JLee, Asan Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Castration-resistant Prostate Cancer Drug: ADT Drug: No ADT Phase 2

Detailed 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : July 2010
Estimated Primary Completion Date : October 2013

Arm Intervention/treatment
Experimental: ADT arm
Concomitant androgen deprivation treatment
Drug: ADT
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

Primary Outcome Measures :
  1. Time to PSA progression [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Composite progression-free survival (PFS) [ Time Frame: 1 year ]
    PFS based on PSA, RECIST, bone scan, and performance status

  2. Overall survival [ Time Frame: 2 year ]
  3. PSA decline [ Time Frame: 12 weeks ]
  4. PSA response to ADT retrial [ Time Frame: 12 weeks ]

    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.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01487902

Contact: Jae-Lyun Lee, MD, PhD 82 2 3010 5977

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         
Sponsors and Collaborators
Asan Medical Center

Additional Information:
Responsible Party: JLee, Associate professor, Asan Medical Center Identifier: NCT01487902     History of Changes
Other Study ID Numbers: UOSG-AMC-0803
First Posted: December 8, 2011    Key Record Dates
Last Update Posted: December 8, 2011
Last Verified: December 2011

Keywords provided by JLee, Asan Medical Center:

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Methylprednisolone Hemisuccinate
Prednisolone acetate
Methylprednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Autonomic Agents
Peripheral Nervous System Agents