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Androgen Deprivation Therapy Prior to Prostatectomy for Patients With Intermediate and High Risk Prostate Cancer

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ClinicalTrials.gov Identifier: NCT01542021
Recruitment Status : Active, not recruiting
First Posted : March 1, 2012
Last Update Posted : March 3, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

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.


Condition or disease Intervention/treatment
Prostate Cancer Prostatic Adenocarcinoma Drug: degarelix injection Drug: androgen deprivation therapy

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 2012
Estimated Primary Completion Date : February 2018
Estimated Study Completion Date : February 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Degarelix
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Untreated patients degarelix injection occur at days 4± 1
Treatment will consist of a single 240 mg injection of degarelix 4 ± 1 day before radical prostatectomy
Drug: degarelix injection
Treatment will consist of a single 240 mg injection of degarelix 4 ± 1 day before radical prostatectomy, depending on treatment arm.
Experimental: Untreated patients degarelix injection occur at days and 7± 1.
Treatment will consist of a single 240 mg injection of degarelix 7±1 day before radical prostatectomy
Drug: degarelix injection
Treatment will consist of a single 240 mg injection of degarelix 7 ± 1 day before radical prostatectomy, depending on treatment arm.
Experimental: treated patients with androgen deprivation
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.
Drug: androgen deprivation therapy
Experimental: Untreated patients degarelix injection occur at days 14±1
Treatment will consist of a single 240 mg injection of degarelix 14±1 day before radical prostatectomy
Drug: degarelix injection
Treatment will consist of a single 240 mg injection of degarelix 7 ± 1 day before radical prostatectomy, depending on treatment arm.


Outcome Measures

Primary Outcome Measures :
  1. 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) [ Time Frame: 2 years ]
    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 :
  1. To explore the association between PTEN status and maximal changes in prostate cancer proliferation and apoptosis rates in patients treated with androgen deprivation therapy [ Time Frame: 2 years ]
    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.

  2. 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). [ Time Frame: 2 years ]
    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.

  3. To discover novel biomarkers and correlates of response [ Time Frame: 2 years ]
    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


Eligibility Criteria

Information from the National Library of Medicine

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

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 ClinicalTrials.gov identifier (NCT number): NCT01542021


Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Ferring Pharmaceuticals
Investigators
Principal Investigator: Dana Rathkopf, MD Memorial Sloan Kettering Cancer Center
More Information

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01542021     History of Changes
Other Study ID Numbers: 11-182
First Posted: March 1, 2012    Key Record Dates
Last Update Posted: March 3, 2017
Last Verified: March 2017

Keywords provided by Memorial Sloan Kettering Cancer Center:
prostate
Degarelix
injections
radical prostatectomy
11-182

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Androgens
Ascorbic Acid
Estrogens, Conjugated (USP)
Methyltestosterone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Vitamins
Micronutrients
Growth Substances
Estrogens
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents