Phase II Trial of Transdermal Estradiol for Hormone Refractory Prostate Cancer

Study Overview
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Brief Summary
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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 the use of transdermal estrogen 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.

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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Transdermal Estradiol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transdermal estradiol<br> | Drug: Transdermal Estradiol<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With PSA Response | PSA Response is a critical outcome measure used to assess the efficacy of treatments for conditions such as prostate cancer. PSA, or Prostate-Specific Antigen. The PSA Response is a measure of the change in PSA levels before and after a specific treatment intervention. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Measure Quality of Life of Participants Receiving Therapy With the Functional Assessment of Cancer Therapy-Prostate Scale (FACT-P). |  | 3 years | 
| Measurable Disease Response Assessment in Participants With Hormone and Chemotherapy Refractory Prostate Cancer |  | 4 years | 
| Time to Progression |  | 3 years | 
| Plateau Level of Estradiol and Testosterone Response in Androgen-Resistant Population With 0.4mg/Day Transdermal Estradiol Patch |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer