Official Title: “Phase II Trial of Transdermal Estradiol in Patients With Hormone Refractory Prostate Cancer”

Multiple trials have shown the efficacy of estrogen therapy in metastatic prostate cancer, and most recently trials have supported the use of transdermal estrogens (patch) in the patient population with a decreased risk of cardiovascular disease as compared to the oral estrogens. We plan to study(estrogen patch) at a dose of 0.4mg qd. We will evaluate the toxicities and measure quality of life. We will assess PSA response and measurable disease response. This will be a trial available to the Cancer Institute of New Jersey Oncology Group. We will enroll a total of 33 patients. We will plan to enroll 10 at CINJ.Patients will wear the patches (4) continuously. We will obtain blood work and clinic evaluations every three weeks. We will assess quality of life through a questionnaire given to patient every three weeks.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment

Study Primary Completion Date: January 2009

Intervention(s) in this Clinical Trial

• Drug: Transdermal Estradiol
  • application of 4 transdermal estradiol patches, each patch releases a dose of 0.1 mg/day for a total dose of 0.4 mg/day. All four patches will be changed every 7 days. This continuous weekly schedule will be followed until the patient goes off-study. The patch will be applied to a clean, dry, intact area of the lower abdomen or the upper quadrant of the buttock. The sites should be rotated weekly. If a patch falls off during the 7 days, a new patch will be applied for the remainder of the 7 day period. At the end of the 7 days all four patches will be changed.

Primary Measures

• To evaluate the antitumor activity, as measured by PSA response rate in patients with hormone and chemotherapy refractory prostate cancer.
  • Time Frame: 4 years
    Safety Issue?: Yes

Secondary Measures

• To evaluate the toxicities of the use of transdermal estradiol in patients with HRPC after initial chemotherapy. To measure quality of life of patients receiving therapy with the Functional Assessment of Cancer Therapy-Prostate scale (FACT-P).
  • Time Frame: 4 years
    Safety Issue?: Yes
• To evaluate measurable disease response in patients with hormone and chemotherapy refractory prostate cancer.
  • Time Frame: 4 years
    Safety Issue?: Yes
• To evaluate time to progression.
  • Time Frame: 4 years
    Safety Issue?: Yes
• To assess the plateau level of estradiol that is attained with the dose of 0.4mg/day given via transdermal estradiol patch and in addition, assess the response on testosterone in the androgen resistant population.
  • Time Frame: 4 years
    Safety Issue?: Yes

Inclusion Criteria

• Patients with metastatic prostate adenocarcinoma, who have failed initial hormone therapy and who have had progression after at least one chemotherapy regimen that included docetaxel. Patients on antiandrogens must have progression after withdrawal of the antiandrogen for 4 weeks (flutamide) or 6 weeks (bicalutamide).
• PSA ≥ 10 ng/ml.
• Patients who have received LHRH agonist therapy for > 1 month must maintain agonist therapy while on-study. Patients who have not received agonist therapy or received <
• 1 month of therapy, may not begin or continue agonist therapy while on-study.
• Age >18 years and an estimated life expectancy of at least 4 months.
• ECOG performance status ≤ 2 (see Appendix B).
• Full recovery from the effects of any prior surgery or radiation therapy within 4 weeks of study entry.
• Serum creatinine ≤ 1.5 x ULN
• Total bilirubin < ULN
• Transaminases (SGOT and/or SGPT) ≤ 2 X institutional upper limit.
• Capacity to give informed, written consent.

Exclusion Criteria

• Any coexisting medical condition precluding full compliance with the study.
• Any history of deep venous thrombosis (DVT) or pulmonary embolus. Patients with a DVT on anticoagulants for ≥ 6 months will be eligible.
• Known CNS metastasis.
• The discontinuation of flutamide or bicalutamide < 4 or 6 weeks respectively.
• History of severe cardiovascular disease (AHA class III or IV; see Appendix C), uncontrolled CHF or life threatening cardiac dysrhythmia in the past 6 months.
• Herbal supplements may not be used while on-study and patients must have discontinued use for ≥ 1 week before entering on-study.
• Patients with a known hypersensitivity to estrogen.
• Triglyceride > 200 mg/dl.
• Prior estramustine.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Medicine and Dentistry New Jersey

Overall Clinical Trial Officials and Contacts

Mark Stein, MD Principal Investigator University of Medicine and Dentistry New Jersey  

Information obtained from ClinicalTrials.gov on October 07, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00176644

Study ID Number: 5247

ClinicalTrials.gov Identifier: NCT00176644

Health Authority: United States: Food and Drug Administration