Phase II Trial of Transdermal Estradiol for Hormone Refractory Prostate Cancer

• Sponsor: University of Medicine and Dentistry of New Jersey (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00176644
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 23
• Locations: 6
• Arm: 1
• Duration (Months): 43
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Transdermal Estradiol	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Transdermal Estradiol in Patients With Hormone Refractory Prostate Cancer
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. To Evaluate the Antitumor Activity, as Measured by PSA Response Rate in Patients With Hormone and Chemotherapy Refractory Prostate Cancer. [4 years]

Secondary Outcome Measures

1. To Measure Quality of Life of Patients Receiving Therapy With the Functional Assessment of Cancer Therapy-Prostate Scale (FACT-P). [4 years]

2. To Evaluate Measurable Disease Response in Patients With Hormone and Chemotherapy Refractory Prostate Cancer. [4 years]

3. To Evaluate Time to Progression. [4 years]

4. 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. [4 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CentraState Healthcare System	Freehold	New Jersey	United States	07728
2	Robert Wood Johnson University Hospital/CINJ at Hamilton	Hamilton	New Jersey	United States	08690
3	Morristown Memorial Hospital	Morristown	New Jersey	United States	07692
4	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
5	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08903
6	Overlook Hospital	Summit	New Jersey	United States	07901

Sponsors and Collaborators

• University of Medicine and Dentistry of New Jersey
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mark Stein, MD, Rutgers, The State University of New Jersey

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Medicine and Dentistry of New Jersey
• ClinicalTrials.gov Identifier: NCT00176644
• Other Study ID Numbers: CDR0000445280; CINJ 080419; P30CA072720; NCT00255632
• First Posted: Sep 15, 2005
• Last Update Posted: Dec 24, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by University of Medicine and Dentistry of New Jersey: prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Estradiol

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from the Cancer Institute of New Jersey (a comprehensive cancer center) and 4 community hospitals within the Cancer Institute of New Jersey Oncology Group from May 2005 through April 2008.

Arm/Group Title	Transdermal Estradiol
Arm/Group Description	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.
Period Title: Overall Study
STARTED	23
COMPLETED	22
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Transdermal Estradiol
Arm/Group Description	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.
Overall Participants	23
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 17.4%
>=65 years	19 82.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.4 (8.2)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	23 100%
Region of Enrollment (participants) [Number]
United States	23 100%

Outcome Measures

1. Primary Outcome

Title	To Evaluate the Antitumor Activity, as Measured by PSA Response Rate in Patients With Hormone and Chemotherapy Refractory Prostate Cancer.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transdermal Estradiol
Arm/Group Description	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.
Measure Participants	23
Number [Response rate (percentage)]	8.7

2. Secondary Outcome

Title	To Measure Quality of Life of Patients Receiving Therapy With the Functional Assessment of Cancer Therapy-Prostate Scale (FACT-P).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Analysis was not conducted as therapy was determined to be ineffective (response rate < 20%).

Arm/Group Title	Transdermal Estradiol
Arm/Group Description	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.
Measure Participants	0

3. Secondary Outcome

Title	To Evaluate Measurable Disease Response in Patients With Hormone and Chemotherapy Refractory Prostate Cancer.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Analysis was not conducted as therapy was determined to be ineffective (response rate < 20%).

Arm/Group Title	Transdermal Estradiol
Arm/Group Description	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.
Measure Participants	0

4. Secondary Outcome

Title	To Evaluate Time to Progression.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Analysis was not conducted as therapy was determined to be ineffective (response rate < 20%).

Arm/Group Title	Transdermal Estradiol
Arm/Group Description	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.
Measure Participants	0

5. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Analysis was not conducted as therapy was determined to be ineffective (response rate < 20%).

Arm/Group Title	Transdermal Estradiol
Arm/Group Description	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.
Measure Participants	0

Adverse Events

Time Frame	3 years and 6 months
Arm/Group Title	Transdermal Estradiol
Arm/Group Description	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.
All Cause Mortality
	Transdermal Estradiol
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Transdermal Estradiol
	Affected / at Risk (%)	# Events
Total	5/23 (21.7%)
Blood and lymphatic system disorders
Hemoglobin	2/23 (8.7%)	2
Platelets	1/23 (4.3%)	1
Gastrointestinal disorders
Constipation	1/23 (4.3%)	1
General disorders
Pain - Bone	1/23 (4.3%)	1
Investigations
AST, SGOT(serum glutamic oxaloacetic transaminase)	1/23 (4.3%)	1
Alkaline phosphatase	1/23 (4.3%)	1
Nervous system disorders
Neuropathy: sensory	1/23 (4.3%)	1
Renal and urinary disorders
Obstruction, GU - Urethra	1/23 (4.3%)	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/23 (4.3%)	1
Other (Not Including Serious) Adverse Events
	Transdermal Estradiol
	Affected / at Risk (%)	# Events
Total	18/23 (78.3%)
Blood and lymphatic system disorders
Hemoglobin	2/23 (8.7%)	5
Edema: limb	3/23 (13%)	5
Gastrointestinal disorders
Nausea	3/23 (13%)	3
Constipation	2/23 (8.7%)	2
General disorders
Pain - Bone	3/23 (13%)	3
Pain - Breast	3/23 (13%)	3
Pain - Extremity-limb	3/23 (13%)	3
Pain - Back	3/23 (13%)	3
Pain - Neck	2/23 (8.7%)	2
Pain - Other (Specify, __)	2/23 (8.7%)	2
Fatigue (asthenia, lethargy, malaise)	5/23 (21.7%)	5
Sweating (diaphoresis)	2/23 (8.7%)	2
Investigations
Albumin, serum-low (hypoalbuminemia)	2/23 (8.7%)	2
Calcium, serum-low (hypocalcemia)	2/23 (8.7%)	2
Nervous system disorders
Neuropathy: sensory	2/23 (8.7%)	2
Reproductive system and breast disorders
Gynecomastia	2/23 (8.7%)	2
Skin and subcutaneous tissue disorders
Pruritus/itching	2/23 (8.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.