The Role of Androgen Deprivation Treatment (ADT) in Docetaxe-Prednisolone Chemotherapy for Castrate-Resistant Prostatic Cancer
Primary Purpose
Castration-resistant Prostate Cancer
Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
ADT
No ADT
Sponsored by
About this trial
This is an interventional treatment trial for Castration-resistant Prostate Cancer focused on measuring Chemotherapy-naive
Eligibility Criteria
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
Sites / Locations
- Asan Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
ADT arm
No ADT arm
Arm Description
Concomitant androgen deprivation treatment
No concomitant androgen deprivation treatment arm
Outcomes
Primary Outcome Measures
Time to PSA progression
Secondary Outcome Measures
Composite progression-free survival (PFS)
PFS based on PSA, RECIST, bone scan, and performance status
Overall survival
PSA decline
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01487902
Brief Title
The Role of Androgen Deprivation Treatment (ADT) in Docetaxe-Prednisolone Chemotherapy for Castrate-Resistant Prostatic Cancer
Official Title
Randomized Phase II Screening Trial of Docetaxel Plus Prednisolone With or Without Androgen Deprivation Treatment in Castrate-Resistant Prostatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
December 2011
Overall Recruitment Status
Unknown status
Study Start Date
July 2010 (undefined)
Primary Completion Date
October 2013 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Castration-resistant Prostate Cancer
Keywords
Chemotherapy-naive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ADT arm
Arm Type
Experimental
Arm Description
Concomitant androgen deprivation treatment
Arm Title
No ADT arm
Arm Type
Active Comparator
Arm Description
No concomitant androgen deprivation treatment arm
Intervention Type
Drug
Intervention Name(s)
ADT
Intervention Description
Luprolide 11.25 mg long-acting depo (Lucrin Depot PDS inj®) every 12 weeks SC wit Docetaxel-prednisolone (TAX327 regimen)
Intervention Type
Drug
Intervention Name(s)
No ADT
Intervention Description
Docetaxel-prednisolone (TAX327 regimen) alone
Primary Outcome Measure Information:
Title
Time to PSA progression
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Composite progression-free survival (PFS)
Description
PFS based on PSA, RECIST, bone scan, and performance status
Time Frame
1 year
Title
Overall survival
Time Frame
2 year
Title
PSA decline
Time Frame
12 weeks
Title
PSA response to ADT retrial
Description
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.
Time Frame
12 weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jae-Lyun Lee, MD, PhD
Phone
82 2 3010 5977
Email
jaelyun@amc.seoul.kr
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hee Jeong Jeon, BSc
First Name & Middle Initial & Last Name & Degree
Jae-Lyun Lee, MD, PhD.
First Name & Middle Initial & Last Name & Degree
Hanjong Ahn, MD, PhD.
First Name & Middle Initial & Last Name & Degree
Jun-Hyuk Hong, MD, PhD.
First Name & Middle Initial & Last Name & Degree
Cheryn Song, MD, PhD.
First Name & Middle Initial & Last Name & Degree
In-Gab Jeong, MD, PhD
12. IPD Sharing Statement
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/20686407
Description
Retrospective study on the role of ADT
Learn more about this trial
The Role of Androgen Deprivation Treatment (ADT) in Docetaxe-Prednisolone Chemotherapy for Castrate-Resistant Prostatic Cancer
We'll reach out to this number within 24 hrs