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

NCT01542021 | Completed

• 1 other identifier: 11-182
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer; Prostatic Adenocarcinoma

Keywords

prostate; Degarelix; injections; radical prostatectomy; 11-182

Outcome Measures

Primary Outcomes (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)

  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.

  2 years

Secondary Outcomes (3)

• To explore the association between PTEN status and maximal changes in prostate cancer proliferation and apoptosis rates in patients treated with androgen deprivation therapy

  2 years

• 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).

  2 years

• To discover novel biomarkers and correlates of response

  2 years

Study Arms (4)

Untreated patients degarelix injection occur at days 4± 1

EXPERIMENTAL

Treatment will consist of a single 240 mg injection of degarelix 4 ± 1 day before radical prostatectomy

Drug: degarelix injection

Untreated patients degarelix injection occur at days and 7± 1.

EXPERIMENTAL

Treatment will consist of a single 240 mg injection of degarelix 7±1 day before radical prostatectomy

Drug: degarelix injection

treated patients with androgen deprivation

EXPERIMENTAL

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

Untreated patients degarelix injection occur at days 14±1

EXPERIMENTAL

Treatment will consist of a single 240 mg injection of degarelix 14±1 day before radical prostatectomy

Drug: degarelix injection

Interventions

degarelix injection DRUG

Treatment will consist of a single 240 mg injection of degarelix 4 ± 1 day before radical prostatectomy, depending on treatment arm.

Untreated patients degarelix injection occur at days 4± 1

androgen deprivation therapy DRUG

treated patients with androgen deprivation

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic confirmation of prostatic adenocarcinoma by MSKCC inclusive of the following:
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Ferring Pharmaceuticals: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 34350976 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Androgen Antagonists

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Dana Rathkopf, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2012
• First Posted: March 1, 2012
• Study Start: February 24, 2012
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: October 3, 2024

Record last verified: 2024-10

Locations

US (1)