Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer

• Sponsor: Jorge A. Garcia, MD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00526591
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 47
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving everolimus before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This randomized phase II trial is studying the side effects and how well everolimus works in treating patients with newly diagnosed localized prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Everolimus; Procedure: conventional surgery	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine the clinical effects of everolimus, in terms of pathologic response (i.e., histologic P0, margin status, or capsular penetration) and surgical outcome, in patients with newly diagnosed localized prostate cancer treated with two different doses of everolimus prior to radical prostatectomy.

• To evaluate the safety and tolerability of this drug in these patients.

Secondary

• To determine the effect of this drug on prostate-specific antigen (PSA) levels in these patients.

• To determine the effect of this drug on levels of expression of PTEN, Akt, phospho-mTOR (i.e., Se2448), phospho-p70 S6 kinase (i.e., Thre389), phospho-Smad3 (i.e., Ser433/435), phospho-Smads 1/5 (i.e., Ser463/465), AR, and TUNEL in these patients.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive low-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.

• Arm II: Patients receive high-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.

Within 7 days after the last dose of everolimus, all patients undergo radical prostatectomy with bilateral pelvic lymphadenectomy.

Tumor biopsy specimens acquired prior to treatment and prostate tumor tissue acquired at the time of radical prostatectomy are evaluated for biomarker correlative studies. Tissue samples are assessed by immunohistochemistry (IHC) and tissue microarray analysis for expression of cellular and molecular biomarkers (i.e., p-S6, p-4E-BP1, and p-Akt) that correlate with response. Prostatectomy specimens are also assessed by pathologic analysis for histopathologic response (i.e., pathologic stage, Gleason score, margin status, and tumor size).

After completion of study therapy, patients are followed at 6 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Study of Two Different Doses of RAD-001 (Everolimus) as Neo-Adjuvant Therapy in Patients With Localized Prostate Cancer
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low-dose Everolimus Cohort 5mg Everolimus daily continuously for 8 weeks and conventional surgery	Drug: Everolimus; Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week; Other Names: RAD-001 ; Procedure: conventional surgery; Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
Active Comparator: High-dose Everolimus Cohort 10mg Everolimus daily continuously for 8 weeks and conventional surgery	Drug: Everolimus; Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week; Other Names: RAD-001 ; Procedure: conventional surgery; Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Who Are P0 (i.e., no Clinically Detectable Tumor in the Pathologic Specimen) at Surgery [After 8 weeks of therapy at the time of prostatectomy]

   Specimens are fixed in formalin for 24 hours.Specimens are the cut at 3 mm intervals perpendicular to the rectal surface and the sections are examined grossly and microscopically on routine Hematoxylin and Eosin stain (H&E) (pathologic complete response or P0) will be defined as responders.

2. Toxicity Profile of Each Dose (Number of Patients With Worst Grade Toxicity) [at daily dose for 8 weeks]

   Toxicity will be assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAEv3.0)

Secondary Outcome Measures

1. Change in PSA [Up to 16 weeks after start of study]

   Time-to-event data, such as change in PSA will be summarized using the method of Kaplan and Meier.

Other Outcome Measures

1. Effect of Treatment on Biological and Molecular Markers [After 8 weeks of therapy]

   Immunohistochemical Staining of Cellular and Molecular Markers in Prostate Tumor Tissue

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed newly diagnosed, localized adenocarcinoma of the prostate, meeting any of the following criteria:

• Clinical stage T2a, T2b, T2c, or T3 disease (any grade or PSA)

• Gleason score 7 (4+3 only) or ≥ 8 (any stage or PSA)

• Serum PSA ≥ 10 ng/dL (any grade or stage)

• Any stage, PSA, or Gleason score AND ≥ 35% chance of biochemical failure at 5 years based on Kattan's nomogram

• Recommended for radical prostatectomy

• Normal testosterone level

• No pure neuroendocrine or small cell prostate cancer

• No metastatic disease by CT scan, MRI, bone scan, or X-ray

• No clinical evidence of CNS metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%

• ANC ≥ 1,500/μL

• Platelet count ≥ 100,000/μL

• Hemoglobin ≥ 8 g/dL

• AST and ALT ≤ 1.5 times upper limit of normal (ULN)

• Bilirubin ≤ 1.5 times ULN

• Creatinine ≤ 1.5 times ULN

• PT/PTT normal (no anticoagulants)

• No active unresolved infection

• No known HIV positivity

• Fertile patients must use effective contraception during and for 6 months after completion of study therapy

Exclusion criteria:

• Known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus or temsirolimus) or to its excipients

• Gastrointestinal (GI) disease, condition, or symptoms that may significantly impair GI function and alter the absorption of everolimus, including any of the following:

• Ulcerative disease

• Uncontrolled nausea

• Vomiting

• Diarrhea

• Malabsorption syndrome

• Other active malignancy or malignancy at ≥ 30% risk for relapse after completion of therapy, except nonmelanoma skin cancer

• Uncontrolled concurrent illness including, but not limited to, any of the following:

• Ongoing or active infection (e.g., bacterial, viral or fungal)

• Severely impaired lung function

• Uncontrolled diabetes (fasting serum glucose > 1.5 times ULN)

• Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis)

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situation that would limit study compliance

• Any underlying medical condition which, in the principal investigator's opinion, will make the administration of everolimus hazardous OR obscure the interpretation of adverse events

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since major surgery

• More than 3 months since finasteride

• No prior or concurrent radiotherapy to the prostate gland or pelvis

• No prior hormones (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, or antiandrogens [e.g., bicalutamide, flutamide, or nilutamide]) and/or PC-SPES (or PC-x product) or estrogen-containing nutraceuticals

• No prior rapamycin mTOR inhibitor

• No prior small bowel resection that may significantly impair GI function and alter the absorption of everolimus

• No prior or concurrent immunotherapy, chemotherapy, or other investigational therapy for prostate cancer

• No other concurrent investigational or commercial agents

• No other concurrent anticancer agents

• No concurrent, chronic treatment with systemic steroids (except inhaled or topical steroids) or another immunosuppressive agent

• No concurrent live vaccines

• No concurrent strong inhibitors or inducers of the isoenzyme CYP3A administered as systemic therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Jorge A. Garcia, MD
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jorge A. Garcia, MD, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jorge A. Garcia, MD, Principal Investigator, Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00526591
• Other Study ID Numbers: CASE21806; P30CA043703; CASE-21806; CASE-21806-CC256
• First Posted: Sep 10, 2007
• Last Update Posted: Dec 6, 2018
• Last Verified: Nov 1, 2018

• Keywords provided by Jorge A. Garcia, MD, Principal Investigator, Case Comprehensive Cancer Center: adenocarcinoma of the prostate; stage I prostate cancer; stage II prostate cancer; stage III prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Everolimus

Study Results

Participant Flow

Arm/Group Title	Low-dose Cohort	High-dose Cohort
Arm/Group Description	Patients will receive 5.0mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).	Patients will receive 10mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
Period Title: Overall Study
STARTED	8	9
COMPLETED	8	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Low-dose Cohort	High-dose Cohort	Total
Arm/Group Description	Patients will receive 5.0mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).	Patients will receive 10mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).	Total of all reporting groups
Overall Participants	8	9	17
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (7.9)	59 (4.5)	59 (6.2)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	9 100%	17 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	9 100%	17 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 12.5%	0 0%	1 5.9%
White	7 87.5%	9 100%	16 94.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	9 100%	17 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Who Are P0 (i.e., no Clinically Detectable Tumor in the Pathologic Specimen) at Surgery
Description	Specimens are fixed in formalin for 24 hours.Specimens are the cut at 3 mm intervals perpendicular to the rectal surface and the sections are examined grossly and microscopically on routine Hematoxylin and Eosin stain (H&E) (pathologic complete response or P0) will be defined as responders.
Time Frame	After 8 weeks of therapy at the time of prostatectomy

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Low-dose Cohort	High-dose Cohort
Arm/Group Description	Patients will receive 5.0mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).	Patients will receive 10mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
Measure Participants	8	9
Number [participants]	0 0%	0 0%

2. Primary Outcome

Title	Toxicity Profile of Each Dose (Number of Patients With Worst Grade Toxicity)
Description	Toxicity will be assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAEv3.0)
Time Frame	at daily dose for 8 weeks

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Low-dose Cohort	High-dose Cohort
Arm/Group Description	Patients will receive 5.0mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).	Patients will receive 10mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
Measure Participants	8	9
Patients with Grade 3 toxicity	2 25%	1 11.1%
Patients with Grade 4 toxicity	0 0%	0 0%

3. Secondary Outcome

Title	Change in PSA
Description	Time-to-event data, such as change in PSA will be summarized using the method of Kaplan and Meier.
Time Frame	Up to 16 weeks after start of study

Outcome Measure Data

Analysis Population Description

One patient in the high dose cohort was not analyzed for change in PSA because they withdrew early due to progressive disease

Arm/Group Title	High-dose Cohort	Low-dose Cohort
Arm/Group Description	Patients will receive 10mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).	Patients will receive 5.0mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
Measure Participants	8	8
Median (Inter-Quartile Range) [ng/mL]	3.5	3.04

4. Other Pre-specified Outcome

Title	Effect of Treatment on Biological and Molecular Markers
Description	Immunohistochemical Staining of Cellular and Molecular Markers in Prostate Tumor Tissue
Time Frame	After 8 weeks of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	At daily dose for 8 weeks
Arm/Group Title	Low-dose Cohort		High-dose Cohort
Arm/Group Description	Patients will receive 5.0mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).		Patients will receive 10mg P.O. daily continuously for 8 weeks everolimus: Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks conventional surgery: Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
All Cause Mortality
	Low-dose Cohort		High-dose Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Low-dose Cohort		High-dose Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/8 (12.5%)	1	0/9 (0%)	0
Other (Not Including Serious) Adverse Events
	Low-dose Cohort		High-dose Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		9/9 (100%)
Blood and lymphatic system disorders
Leukocytes (total WBC)	0/8 (0%)	0	5/9 (55.6%)	5
Lymphopenia	0/8 (0%)	0	4/9 (44.4%)	5
Eye disorders
Dry eye syndrome	2/8 (25%)	2	0/9 (0%)	0
Gastrointestinal disorders
Constipation	1/8 (12.5%)	1	0/9 (0%)	0
Diarrhea	1/8 (12.5%)	1	1/9 (11.1%)	1
Distension/bloating, abdominal	1/8 (12.5%)	1	0/9 (0%)	0
Dry mouth/salivary gland (xerostomia)	1/8 (12.5%)	1	0/9 (0%)	0
Heartburn/dyspepsia	1/8 (12.5%)	1	1/9 (11.1%)	1
Hemorrhage, GI - Rectum	1/8 (12.5%)	1	0/9 (0%)	0
Hemorrhoids	1/8 (12.5%)	1	0/9 (0%)	0
Mucositis/stomatitis (clinical exam) - Oral cavity	5/8 (62.5%)	11	7/9 (77.8%)	12
Nausea	3/8 (37.5%)	3	1/9 (11.1%)	1
abdominal pain	2/8 (25%)	2	0/9 (0%)	0
Pain broken tooth	1/8 (12.5%)	1	0/9 (0%)	0
pain/rectal	0/8 (0%)	0	1/9 (11.1%)	1
General disorders
Sensation of coldness	1/8 (12.5%)	1	0/9 (0%)	0
Edema: limb	1/8 (12.5%)	1	3/9 (33.3%)	5
Fatigue (asthenia, lethargy, malaise)	5/8 (62.5%)	6	3/9 (33.3%)	5
Pain - Chest/thorax NOS	2/8 (25%)	2	0/9 (0%)	0
Flu-like syndrome	0/8 (0%)	0	1/9 (11.1%)	1
Rigors/chills	0/8 (0%)	0	1/9 (11.1%)	1
Sweating (diaphoresis)	0/8 (0%)	0	1/9 (11.1%)	1
Infections and infestations
infection	1/8 (12.5%)	1	0/9 (0%)	0
Pharyngitis	1/8 (12.5%)	1	0/9 (0%)	0
Stabbing rectal pain Infection with normal ANC	1/8 (12.5%)	1	0/9 (0%)	0
Infection, lower lip	0/8 (0%)	0	1/9 (11.1%)	1
Injury, poisoning and procedural complications
Wound complication, non-infectious	2/8 (25%)	2	0/9 (0%)	0
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	0/8 (0%)	0	1/9 (11.1%)	1
Investigations
Aspartate aminotransferase	4/8 (50%)	4	2/9 (22.2%)	2
hemoglobin	1/8 (12.5%)	1	5/9 (55.6%)	5
Cholesterol high	5/8 (62.5%)	7	4/9 (44.4%)	4
Creatinine	1/8 (12.5%)	1	1/9 (11.1%)	1
Weight loss	1/8 (12.5%)	1	1/9 (11.1%)	1
ALT, SGPT (serum glutamic pyruvic transaminase)	0/8 (0%)	0	1/9 (11.1%)	1
Bicarbonate, serum-low	0/8 (0%)	0	1/9 (11.1%)	1
Neutrophils/granulocytes (ANC/AGC)	0/8 (0%)	0	2/9 (22.2%)	2
Pain at surgery site	0/8 (0%)	0	1/9 (11.1%)	1
Platelets	0/8 (0%)	0	5/9 (55.6%)	6
Metabolism and nutrition disorders
Anorexia	1/8 (12.5%)	2	3/9 (33.3%)	3
Dehydration	1/8 (12.5%)	2	0/9 (0%)	0
Glucose, serum-high (hyperglycemia)	5/8 (62.5%)	7	2/9 (22.2%)	2
Phosphate, serum-low (hypophosphatemia)	1/8 (12.5%)	2	5/9 (55.6%)	5
Triglyceride, serum-high (hypertriglyceridemia)	3/8 (37.5%)	5	5/9 (55.6%)	5
Uric acid, serum-high (hyperuricemia)	1/8 (12.5%)	1	0/9 (0%)	0
Calcium, serum-low (hypocalcemia)	0/8 (0%)	0	1/9 (11.1%)	1
Potassium, serum-high (hyperkalemia)	0/8 (0%)	0	4/9 (44.4%)	4
Uric acid, serum-high (hyperuricemia)	0/8 (0%)	0	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
Pain - Back	1/8 (12.5%)	1	0/9 (0%)	0
Pain, left heel	0/8 (0%)	0	1/9 (11.1%)	1
Nervous system disorders
Dizziness	1/8 (12.5%)	1	0/9 (0%)	0
Pain - Head/headache	3/8 (37.5%)	3	3/9 (33.3%)	4
Taste alteration (dysgeusia)	0/8 (0%)	0	2/9 (22.2%)	2
Psychiatric disorders
insominia	1/8 (12.5%)	1	0/9 (0%)	0
libido	1/8 (12.5%)	1	0/9 (0%)	0
Renal and urinary disorders
Incontinence, urinary	7/8 (87.5%)	8	4/9 (44.4%)	4
Urinary frequency/urgency	1/8 (12.5%)	1	1/9 (11.1%)	1
Urinary retention (including neurogenic bladder)	1/8 (12.5%)	1	0/9 (0%)	0
Pain and burning while urinating	0/8 (0%)	0	1/9 (11.1%)	1
nocturia	0/8 (0%)	0	3/9 (33.3%)	3
Reproductive system and breast disorders
Erectile dysfunction	3/8 (37.5%)	3	1/9 (11.1%)	1
Pain, left groin	0/8 (0%)	0	1/9 (11.1%)	1
pain,left groin	0/8 (0%)	0	1/9 (11.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/8 (25%)	2	0/9 (0%)	0
bronchial mucous	1/8 (12.5%)	1	0/9 (0%)	0
Pain, throat	0/8 (0%)	0	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
dry skin	1/8 (12.5%)	1	1/9 (11.1%)	1
Rash	1/8 (12.5%)	1	1/9 (11.1%)	1
Furuncle	1/8 (12.5%)	1	0/9 (0%)	0
Pruritus/itching	1/8 (12.5%)	1	2/9 (22.2%)	2
Rash/desquamation	2/8 (25%)	2	3/9 (33.3%)	3
Hair Color change	0/8 (0%)	0	1/9 (11.1%)	1
Rash: acne/acneiform	0/8 (0%)	0	3/9 (33.3%)	3
Vascular disorders
Hot flashes/flushes	0/8 (0%)	0	1/9 (11.1%)	1

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.