Back to resultsAndrogen Deprivation Therapy Prior to Prostatectomy for Patients With Intermediate and High Risk Prostate Cancer
Primary Purpose
Prostate Cancer, Prostatic Adenocarcinoma
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
degarelix injection
degarelix injection
androgen deprivation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring prostate, Degarelix, injections, radical prostatectomy, 11-182
Eligibility Criteria
Inclusion Criteria:
- Histologic confirmation of prostatic adenocarcinoma by MSKCC inclusive of the following:
- 3 or more positive biopsy cores or equivalent tumor specimen as confirmed by pathologist
- At least 2 cores containing ≥3 mm of tissue with carcinoma or equivalent tumor specimen as confirmed by pathologist
- A primary tumor Gleason score ≥ 7
- Adequate primary biopsy tissue or equivalent tumor specimen as confirmed by pathologist available for protocol required analysis (i.e. bladder or TURP specimen)
- Planning to have or have had a radical prostatectomy (RP) at MSKCC
- Candidates may have a history of deep vein thrombosis, pulmonary embolism, and/or cerebrovascular accident, or require concomitant systemic anticoagulation, if otherwise deemed to be suitable for RP
- Karnofsky performance status >70% (Appendix A)
- Sexually active fertile subjects, and their partners, must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 3 months after the dose of study drug(s) for Cohorts 1 , 2 and 4, and for 3 months after the surgery for Cohort 3
- For cohorts 1,2 and 4 only:, non-castrate testosterone level (>100 ng/dL)
- For cohort 3 only:, 1-6 months of androgen deprivation therapy (gonadotropin hormone releasing analogs with or without an anti-androgen) prior to prostatectomy with a castrate testosterone level of <50 ng/dL within 1 month prior to prostatectomy.
Exclusion Criteria:
- Histologic variants in the primary tumor (histologic variants other than adenocarcinoma)
- Current or prior chemotherapy
- The use of the 5-alpha-reductase inhibitor dutasteride must be discontinued within 4 weeks of degarelix injection for Cohort 1, 2 and 4, and within 4 weeks of surgery for Cohort 3.
- Saw palmetto administered with the intent to treat the patient's malignancy within 1 week of degarelix injection for Cohorts 1, 2 and 4, and for within 1 week of surgery for Cohort 3
- Current or prior radiation therapy to the prostate
- Active infection or intercurrent illness
- Concomitant therapy with any other experimental drug
- For cohorts 1, 2 and 4 only:, current or prior hormonal therapy (e.g., gonadotropin hormone releasing analogs, megestrol acetate, or antiandrogens) are exclusionary
Sites / Locations
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Untreated patients degarelix injection occur at days 4± 1
Untreated patients degarelix injection occur at days and 7± 1.
treated patients with androgen deprivation
Untreated patients degarelix injection occur at days 14±1
Arm Description
Treatment will consist of a single 240 mg injection of degarelix 4 ± 1 day before radical prostatectomy
Treatment will consist of a single 240 mg injection of degarelix 7±1 day before radical prostatectomy
Patients already treated with androgen deprivation are assigned to Cohort 3 and maintained on current androgen deprivation therapy until they undergo or have already undergone RP at MSKCC. Will include patients who have already undergone hormonal therapy (of any duration between 1 and 6 months) prior to prostatectomy.
Treatment will consist of a single 240 mg injection of degarelix 14±1 day before radical prostatectomy
Outcomes
Primary Outcome Measures
To assess between the time to determine the time of the maximal change in prostate cancer cell proliferation (Ki-67) and apoptosis rates (cleaved caspase-3)
The primary endpoint is the change in the rate of proliferation (Ki-67) and the rate of apoptosis (cleaved caspase-3), as evaluated by IHC in anatomically matched tumor foci from the pre-treatment diagnostic biopsy and the RP specimen. The levels in pre-treatment biopsy serve as the baseline. Ki-67 is a widely accepted nuclear marker for cell proliferation. Cleaved caspase-3 has been shown to be a reliable marker of apoptosis and correlate with results from other apoptosis markers such as cleaved PARP-1 and TUNEL assay.
Secondary Outcome Measures
To explore the association between PTEN status and maximal changes in prostate cancer proliferation and apoptosis rates in patients treated with androgen deprivation therapy
The secondary endpoint is PTEN status by IHC in the diagnostic biopsy and RP specimens. PTEN status will be determined by an IHC method that has been validated using control prostate cell lines and tissues at MSKCC. The PTEN status will be reported in binary fashion as "retained" (diffuse moderate immunoreactivity retained in benign glands as well as adenocarcinoma on 100X magnification) or "null" (complete loss of nuclear and cytoplasmic immunoreactivity in tumor cells while expression is retained in surrounding stroma.
To explore the association between PI3K pathway (pAKT and pS6) and prostate cancer proliferation and apoptosis rates after treatment with androgen deprivation therapy in relation to other markers of prostate cancer (ERG, AR and NCOA2).
Additional exploratory endpoints include IHC staining for markers of PI3K pathway (pAKT and pS6) as well as other markers of prostate cancer (ERG, AR and NCOA2) in the diagnostic biopsy and RP specimens. Some of these markers have been validated at MSKCC (pS6, ERG), while others (AR, pAKT, NCOA2) are currently being validated and standardized for the study using appropriate cell line and tissue controls. A general semiquantitative scoring method will be used for these markers.
To discover novel biomarkers and correlates of response
through expression profiling of prostate cancer after three time intervals of androgen deprivation therapy and correlate with PTEN and ERG status, proliferation rate, apoptotic rate, and histologic response
Full Information
NCT ID
NCT01542021
First Posted
February 24, 2012
Last Updated
February 28, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Ferring Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01542021
Brief Title
Androgen Deprivation Therapy Prior to Prostatectomy for Patients With Intermediate and High Risk Prostate Cancer
Official Title
Establishing a Neo-Adjuvant Platform for Developing Targeted Agents: Androgen Deprivation Therapy Prior to Prostatectomy for Patients With Intermediate and High Risk Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2012 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Ferring Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
Degarelix is an approved drug that is used to treat prostate cancer by lowering testosterone levels in the body.
Degarelix is commonly given with radiation for prostate cancer, but less frequently with surgery since there has been no proven benefit with this approach.
The investigators do not expect the patient to benefit directly from treatment with degarelix since their prostate will be removed shortly after the drug is given. Instead, the investigators hope to learn about how degarelix and other treatment that lowers your testosterone effects prostate cancer cells and use this information to develop better treatments in the future.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Prostatic Adenocarcinoma
Keywords
prostate, Degarelix, injections, radical prostatectomy, 11-182
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Untreated patients degarelix injection occur at days 4± 1
Arm Type
Experimental
Arm Description
Treatment will consist of a single 240 mg injection of degarelix 4 ± 1 day before radical prostatectomy
Arm Title
Untreated patients degarelix injection occur at days and 7± 1.
Arm Type
Experimental
Arm Description
Treatment will consist of a single 240 mg injection of degarelix 7±1 day before radical prostatectomy
Arm Title
treated patients with androgen deprivation
Arm Type
Experimental
Arm Description
Patients already treated with androgen deprivation are assigned to Cohort 3 and maintained on current androgen deprivation therapy until they undergo or have already undergone RP at MSKCC. Will include patients who have already undergone hormonal therapy (of any duration between 1 and 6 months) prior to prostatectomy.
Arm Title
Untreated patients degarelix injection occur at days 14±1
Arm Type
Experimental
Arm Description
Treatment will consist of a single 240 mg injection of degarelix 14±1 day before radical prostatectomy
Intervention Type
Drug
Intervention Name(s)
degarelix injection
Intervention Description
Treatment will consist of a single 240 mg injection of degarelix 4 ± 1 day before radical prostatectomy, depending on treatment arm.
Intervention Type
Drug
Intervention Name(s)
degarelix injection
Intervention Description
Treatment will consist of a single 240 mg injection of degarelix 7 ± 1 day before radical prostatectomy, depending on treatment arm.
Intervention Type
Drug
Intervention Name(s)
androgen deprivation therapy
Primary Outcome Measure Information:
Title
To assess between the time to determine the time of the maximal change in prostate cancer cell proliferation (Ki-67) and apoptosis rates (cleaved caspase-3)
Description
The primary endpoint is the change in the rate of proliferation (Ki-67) and the rate of apoptosis (cleaved caspase-3), as evaluated by IHC in anatomically matched tumor foci from the pre-treatment diagnostic biopsy and the RP specimen. The levels in pre-treatment biopsy serve as the baseline. Ki-67 is a widely accepted nuclear marker for cell proliferation. Cleaved caspase-3 has been shown to be a reliable marker of apoptosis and correlate with results from other apoptosis markers such as cleaved PARP-1 and TUNEL assay.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
To explore the association between PTEN status and maximal changes in prostate cancer proliferation and apoptosis rates in patients treated with androgen deprivation therapy
Description
The secondary endpoint is PTEN status by IHC in the diagnostic biopsy and RP specimens. PTEN status will be determined by an IHC method that has been validated using control prostate cell lines and tissues at MSKCC. The PTEN status will be reported in binary fashion as "retained" (diffuse moderate immunoreactivity retained in benign glands as well as adenocarcinoma on 100X magnification) or "null" (complete loss of nuclear and cytoplasmic immunoreactivity in tumor cells while expression is retained in surrounding stroma.
Time Frame
2 years
Title
To explore the association between PI3K pathway (pAKT and pS6) and prostate cancer proliferation and apoptosis rates after treatment with androgen deprivation therapy in relation to other markers of prostate cancer (ERG, AR and NCOA2).
Description
Additional exploratory endpoints include IHC staining for markers of PI3K pathway (pAKT and pS6) as well as other markers of prostate cancer (ERG, AR and NCOA2) in the diagnostic biopsy and RP specimens. Some of these markers have been validated at MSKCC (pS6, ERG), while others (AR, pAKT, NCOA2) are currently being validated and standardized for the study using appropriate cell line and tissue controls. A general semiquantitative scoring method will be used for these markers.
Time Frame
2 years
Title
To discover novel biomarkers and correlates of response
Description
through expression profiling of prostate cancer after three time intervals of androgen deprivation therapy and correlate with PTEN and ERG status, proliferation rate, apoptotic rate, and histologic response
Time Frame
2 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologic confirmation of prostatic adenocarcinoma by MSKCC inclusive of the following:
3 or more positive biopsy cores or equivalent tumor specimen as confirmed by pathologist
At least 2 cores containing ≥3 mm of tissue with carcinoma or equivalent tumor specimen as confirmed by pathologist
A primary tumor Gleason score ≥ 7
Adequate primary biopsy tissue or equivalent tumor specimen as confirmed by pathologist available for protocol required analysis (i.e. bladder or TURP specimen)
Planning to have or have had a radical prostatectomy (RP) at MSKCC
Candidates may have a history of deep vein thrombosis, pulmonary embolism, and/or cerebrovascular accident, or require concomitant systemic anticoagulation, if otherwise deemed to be suitable for RP
Karnofsky performance status >70% (Appendix A)
Sexually active fertile subjects, and their partners, must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 3 months after the dose of study drug(s) for Cohorts 1 , 2 and 4, and for 3 months after the surgery for Cohort 3
For cohorts 1,2 and 4 only:, non-castrate testosterone level (>100 ng/dL)
For cohort 3 only:, 1-6 months of androgen deprivation therapy (gonadotropin hormone releasing analogs with or without an anti-androgen) prior to prostatectomy with a castrate testosterone level of <50 ng/dL within 1 month prior to prostatectomy.
Exclusion Criteria:
Histologic variants in the primary tumor (histologic variants other than adenocarcinoma)
Current or prior chemotherapy
The use of the 5-alpha-reductase inhibitor dutasteride must be discontinued within 4 weeks of degarelix injection for Cohort 1, 2 and 4, and within 4 weeks of surgery for Cohort 3.
Saw palmetto administered with the intent to treat the patient's malignancy within 1 week of degarelix injection for Cohorts 1, 2 and 4, and for within 1 week of surgery for Cohort 3
Current or prior radiation therapy to the prostate
Active infection or intercurrent illness
Concomitant therapy with any other experimental drug
For cohorts 1, 2 and 4 only:, current or prior hormonal therapy (e.g., gonadotropin hormone releasing analogs, megestrol acetate, or antiandrogens) are exclusionary
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dana Rathkopf, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34350976
Citation
Zengerling F, Jakob JJ, Schmidt S, Meerpohl JJ, Blumle A, Schmucker C, Mayer B, Kunath F. Degarelix for treating advanced hormone-sensitive prostate cancer. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD012548. doi: 10.1002/14651858.CD012548.pub2.
Results Reference
derived
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
Androgen Deprivation Therapy Prior to Prostatectomy for Patients With Intermediate and High Risk Prostate Cancer
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