Phase II Trial of Transdermal Estradiol for Hormone Refractory Prostate Cancer

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 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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Transdermal Estradiol

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • CentraState Healthcare System
    • Hamilton, New Jersey, United States, 08690
      • Robert Wood Johnson University Hospital/CINJ at Hamilton
    • Morristown, New Jersey, United States, 07692
      • Morristown Memorial Hospital
    • New Brunswick, New Jersey, United States, 08901
      • Cancer Institute Of New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Saint Peter's University Hospital
    • Summit, New Jersey, United States, 07901
      • Overlook Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Transdermal estradiol

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.

What is the study measuring?

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	Time Frame
Time to Progression	3 years
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
Plateau Level of Estradiol and Testosterone Response in Androgen-Resistant Population With 0.4mg/Day Transdermal Estradiol Patch	3 years

Collaborators and Investigators

• Sponsor: University of Medicine and Dentistry of New Jersey
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mark Stein, MD, Rutgers, The State University of New Jersey

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimated): September 15, 2005

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: CDR0000445280; P30CA072720 (U.S. NIH Grant/Contract); CINJ 080419 (Other Identifier: Cancer Institute of New Jersey)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO