Zometa on Bone Mineral Density in Prostate Cancer Patients Undergoing Androgen Ablation Therapy

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Completed
• CT.gov ID: NCT00582556
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 44
• Location: 1
• Arms: 3
• Duration (Months): 119
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this research is to determine the effect of timing of Zometa® administration on bone mineral density of the lumbar spine and femoral neck in men undergoing androgen deprivation therapy for prostate adenocarcinoma. In addition, the researchers will also determine the effects of treatment with Zometa® on peripheral blood markers of bone turnover, on peripheral blood gd T-cell frequencies and function, and to determine if the above treatments elicit prostate antigen-specific IgG immune responses. The effects of the above treatments on serial serum PSA measurements will also be examined.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Zometa; Drug: zometa; Drug: Zometa	Phase 2

Detailed Description

Castration by GnRH agonist therapy with or without androgen antagonists has been a mainstay for advanced prostate cancer. One of the most significant side effects of the use of androgen ablative therapies has been a decrease in bone mineral density, potentially placing patients at greater risk of osteoporosis and bone fractures. It is prudent to anticipate this adverse effect of therapy and to minimize its severity with appropriate and timely pharmacologic intervention. Zometa is a bisphosphonates and bisphosphonates are effective inhibitors of osteoclastic bone resorption. Recent studies have shown that other bisphosphonates were able to reduce the bone loss observed after 24 and 48 weeks of treatment with a GnRH analogue. An unanswered question remains, however, in how frequently these agents should be employed in clinical practice.

This is a three-arm randomized trial of Zometa® on bone mineral density in subjects with stage D prostate cancer undergoing androgen ablation therapy. If subjects are enrolled in Arm 1, the GnRH analogue would be administered every 3 months for 1 year. Four milligrams of Zometa® would be administered IV over 15 minutes 7 days prior to beginning androgen deprivation therapy. If subjects are enrolled in Arm 2, the GnRH analogue would be administered every 3 months for one year, and 4 mg of Zometa® would be administered IV over 15 minutes at month 6. If subjects are enrolled in Arm 3, the GnRH analogue is administered every 3 months for 1 year, with 4 mg of Zometa® administered IV over 15 minutes monthly for 6 months, beginning at month 6.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Zometa on Bone Mineral Density on Patients With Stage D Prostate Cancer Undergoing Androgen Ablation Therapy
• Study Start Date: Apr 1, 2003
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy	Drug: Zometa; GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy; Other Names: zoledronic acid lupron zolodex
Active Comparator: 2 GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given at mo 6	Drug: zometa; GnRH analogue 3-mo depot - q3 months for 1 yr andZometa 4 mg IV over 15 min x 1, given at mo 6; Other Names: zoledronic acid lupron zolodex
Active Comparator: 3 GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6.	Drug: Zometa; GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6.; Other Names: zolodronic acid lupron zolodex

Outcome Measures

Primary Outcome Measures

1. The Number of Subjects Who Had Either an Increase or Decrease on Bone Mineral Density of the Lumbar Spine and Femoral Neck in Men Undergoing Androgen Deprivation Therapy for Prostate Adenocarcinoma. [2 years]

   Effects on bone mineral density were measured at four locations at six month intervals for 24 months.

Secondary Outcome Measures

1. The Number of Subjects Who Had a Significant Increase of Peripheral Blood Markers of Bone Turnover. [2 years]

   Serum bone-specific alkaline phosphatase was collected as the blood marker of bone turnover.

2. Number of Subjects Had a Significant Change in Immune Markers. [2 Years]

   Immune markers were measured by isolating gamma-delta T cells one month after treatment with zoledronic acid.

3. Number of Subjects With Decreases in Prostate Specific Antigen (PSA) After Zoledronic Acid Prior to Beginning Androgen Deprivation Therapy [2 Years]

   PSA response was measured by observing the serum PSA one week after beginning zoledronic acid and prior to beginning androgen deprivation therapy. Arm 2 and Arm 3 were not able to be assessed for this endpoint as all subjects were on androgen deprivation prior to receiving zoledronic acid.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Must have a histologic diagnosis of adenocarcinoma of the prostate.

• For patients without clinical metastasis treated by surgery, serum PSA values must be

0.2 ng/ml by two measurements at least two weeks apart. In patients treated with ablative radiation therapy without clinical metastasis, three consecutive increases in serum PSA must be documented, with at least a one-month interval between values with the final PSA > 2ng/m as evidence of biochemical PSA failure. P

• Patients who have not had prior primary therapy such as radiation or surgery, are required to have a detectable PSA of at least 0.2 ng/ml.

• Patients with evidence of metastatic disease are eligible irrespective of serum PSA level.

• Prior history of a second malignancy is allowed if treated with curative intent and patient has been free of disease greater than five years

• ECOG performance status of < 2.

Exclusion Criteria:

• Prior treatment with a GnRH analogue or anti-androgen.

• Evidence of immunosuppression or have been treated with immunosuppressive therapy, such as chemotherapy, chronic treatment dose corticosteroids, or radiation therapy to bones, within 6 months of study enrollment

• Current or treatment within 4 weeks with estrogen or estrogenic agents (including herbal compound PC-SPES)

• Current or treatment within 4 weeks with herbal compounds for prostate cancer such as PC-SPES or saw palmetto

• Current or treatment within 4 weeks with megestrol

• Current or prior treatment with a bisphosphonate, calcitonin, or other bone resorptive/anabolic agents

• Current use of oral corticosteroids or any such use within the past 6 months

• Current use of potentially bone-toxic anticonvulsants (phenytoin, or carbamazepine)

• History of orchiectomy

• Hypocalcemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Douglas McNeel, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT00582556
• Other Study ID Numbers: CO02807; CO02807; 2003-057; A534260; SMPH/MEDICINE; NCI-2011-00712
• First Posted: Dec 28, 2007
• Last Update Posted: Nov 26, 2019
• Last Verified: Jun 1, 2014

• Keywords provided by University of Wisconsin, Madison: bone mineral density
• Additional relevant MeSH terms: Prostatic Neoplasms; Zoledronic Acid; Leuprolide

Study Results

Participant Flow

Recruitment Details	Subjects were screened and enrolled at the University of Wisconsin Carbone Cancer Center from April 2003 until March 2011.
Pre-assignment Detail	Of the 44 subjects enrolled, one withdrew from the study prior to receiving any study treatment. As a result there were 43 subjects who received at least one dose of study medication.

Arm/Group Title	Zometa Given 7 Days Prior to Beginning ADT	Zometa Given at Month 6	Zometa Given Monthly x 6 Months
Arm/Group Description	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given at mo 6	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6.
Period Title: Overall Study
STARTED	14	15	14
COMPLETED	14	14	12
NOT COMPLETED	0	1	2

Baseline Characteristics

Arm/Group Title	Zometa Given 7 Days Prior to Beginning ADT	Zometa Given at Month 6	Zometa Given Monthly x 6 Months	Total
Arm/Group Description	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given at mo 6	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6.	Total of all reporting groups
Overall Participants	14	15	14	43
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	11 78.6%	11 73.3%	10 71.4%	32 74.4%
>=65 years	3 21.4%	4 26.7%	4 28.6%	11 25.6%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	14 100%	15 100%	14 100%	43 100%
Gleason Score of 8 or more (participants) [Number]
Number [participants]	3 21.4%	4 26.7%	8 57.1%	15 34.9%
Participants with evidence of osteopenia/osteoporosis (participants) [Number]
Number [participants]	6 42.9%	4 26.7%	5 35.7%	15 34.9%

Outcome Measures

1. Primary Outcome

Title	The Number of Subjects Who Had Either an Increase or Decrease on Bone Mineral Density of the Lumbar Spine and Femoral Neck in Men Undergoing Androgen Deprivation Therapy for Prostate Adenocarcinoma.
Description	Effects on bone mineral density were measured at four locations at six month intervals for 24 months.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zometa Given 7 Days Prior to Beginning ADT	Zometa Given at Month 6	Zometa Given Monthly, Months 6-11
Arm/Group Description	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given at mo 6	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6.
Measure Participants	14	15	15
Number [participants]	14 100%	15 100%	15 107.1%

2. Secondary Outcome

Title	The Number of Subjects Who Had a Significant Increase of Peripheral Blood Markers of Bone Turnover.
Description	Serum bone-specific alkaline phosphatase was collected as the blood marker of bone turnover.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zometa Given 7 Days Prior to Beginning ADT	Zometa Given at Month 6	Zometa Given Monthly, Months 6-11
Arm/Group Description	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given at mo 6	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6.
Measure Participants	14	15	15
Number [participants]	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Number of Subjects Had a Significant Change in Immune Markers.
Description	Immune markers were measured by isolating gamma-delta T cells one month after treatment with zoledronic acid.
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zometa Given 7 Days Prior to Beginning ADT	Zometa Given at Month 6	Zometa Given Monthly, Months 6-11
Arm/Group Description	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given at mo 6	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6.
Measure Participants	14	15	15
Number [participants]	0 0%	0 0%	0 0%

4. Secondary Outcome

Title	Number of Subjects With Decreases in Prostate Specific Antigen (PSA) After Zoledronic Acid Prior to Beginning Androgen Deprivation Therapy
Description	PSA response was measured by observing the serum PSA one week after beginning zoledronic acid and prior to beginning androgen deprivation therapy. Arm 2 and Arm 3 were not able to be assessed for this endpoint as all subjects were on androgen deprivation prior to receiving zoledronic acid.
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zometa Given 7 Days Prior to Beginning ADT	Zometa Given at Month 6	Zometa Given Monthly, Months 6-11
Arm/Group Description	Gonadotropin releasing hormone (GnRH) analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given at mo 6	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6.
Measure Participants	14	0	0
Number [participants]	0 0%

Adverse Events

Time Frame	6 years and 7 months
Arm/Group Title	Zometa Given 7 Days Prior to Beginning ADT		Zometa Given at Month 6		Zometa Given Monthly x 6 Months
Arm/Group Description	GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy		GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given at mo 6		GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6.
All Cause Mortality
	Zometa Given 7 Days Prior to Beginning ADT		Zometa Given at Month 6		Zometa Given Monthly x 6 Months
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Zometa Given 7 Days Prior to Beginning ADT		Zometa Given at Month 6		Zometa Given Monthly x 6 Months
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)		2/15 (13.3%)		2/15 (13.3%)
Blood and lymphatic system disorders
Low Platelets	1/14 (7.1%)	1	0/15 (0%)	0	0/14 (0%)	0
Cardiac disorders
Cardiac ischemia/infarction	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
Gastrointestinal disorders
Nausea	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
Vomiting	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
General disorders
Chest Pain (non-cardiac and non-pleuritic)	1/14 (7.1%)	1	0/15 (0%)	1	0/14 (0%)	0
Infections and infestations
Infection without neutropenia	0/14 (0%)		1/15 (6.7%)	1	0/14 (0%)	1
Pulmonary-Other (pneumonia)	0/14 (0%)		0/15 (0%)		1/15 (6.7%)	1
Metabolism and nutrition disorders
Creatine phosphokinase	1/14 (7.1%)	1	0/15 (0%)	1	0/14 (0%)	1
Hypercalcemia	1/14 (7.1%)	1	0/15 (0%)	1	0/14 (0%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other (Complication of prior hip replacement)	1/14 (7.1%)	1	0/15 (0%)	1	0/14 (0%)	1
Musculoskeletal-Other (fracture)	0/14 (0%)		1/15 (6.7%)	1	0/14 (0%)	1
Musculoskeletal-other (shoulder)	1/14 (7.1%)	1	0/15 (0%)	1	0/14 (0%)	1
Right Hip Replacement	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
Pain - abdomen	0/14 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Nervous system disorders
Syncope (fainting)	1/14 (7.1%)	1	1/15 (6.7%)	1	0/15 (0%)	0
Renal and urinary disorders
Creatinine	1/14 (7.1%)	1	0/15 (0%)	1	0/14 (0%)	1
Vascular disorders
Epidural hematoma	0/14 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Zometa Given 7 Days Prior to Beginning ADT		Zometa Given at Month 6		Zometa Given Monthly x 6 Months
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/14 (100%)		15/15 (100%)		15/15 (100%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
Cardiac disorders
Edema	3/14 (21.4%)	3	5/15 (33.3%)	5	2/15 (13.3%)	2
Hypertension	1/14 (7.1%)	1	1/15 (6.7%)	1	0/15 (0%)	0
Hypotension	0/14 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Ear and labyrinth disorders
Auditory/Hearing-Other (hearing loss from broken vessel in ear)	0/14 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Endocrine disorders
Hot flashes	11/14 (78.6%)	14	11/15 (73.3%)	13	11/15 (73.3%)	14
Eye disorders
Blurred vision	1/14 (7.1%)	1	0/15 (0%)	0	1/15 (6.7%)	1
Vision - flashing lights/floaters	0/14 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Gastrointestinal disorders
Abdominal pain or cramping	0/14 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Nausea	1/14 (7.1%)	4	1/15 (6.7%)	1	6/15 (40%)	8
Constipation	1/14 (7.1%)	1	3/15 (20%)	3	3/15 (20%)	4
Diarrhea patients without colostomy	0/14 (0%)	0	2/15 (13.3%)	2	3/15 (20%)	3
Anorexia	2/14 (14.3%)	2	0/15 (0%)	0	1/15 (6.7%)	1
Vomiting	1/14 (7.1%)	1	0/15 (0%)	0	2/15 (13.3%)	2
Salivary Gland Changes	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
Stomatitis/pharyngitis	0/14 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Taste Disturbance (dysgeusia)	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
General disorders
Fatigue	6/14 (42.9%)	6	8/15 (53.3%)	9	7/15 (46.7%)	12
Fever (in the absence of neutropenia)	2/14 (14.3%)	2	0/15 (0%)	0	0/15 (0%)	0
Rigors (chills)	0/14 (0%)	0	1/15 (6.7%)	2	1/15 (6.7%)	1
Sweating (diaphoresis)	1/14 (7.1%)	1	0/15 (0%)	0	1/15 (6.7%)	1
Constitutional Symptoms	0/14 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Infections and infestations
Infection without neutropenia	1/14 (7.1%)	2	3/15 (20%)	3	3/15 (20%)	4
Infection with unknown ANC	0/14 (0%)	0	1/15 (6.7%)	1	1/15 (6.7%)	1
Investigations
weight gain	1/14 (7.1%)	1	1/15 (6.7%)	1	2/15 (13.3%)	3
Weight loss	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
Creatine phosphokinase	1/14 (7.1%)	3	0/15 (0%)	0	0/15 (0%)	0
Hypercalcemia	0/14 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Hyperglycemia	0/14 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Low Hemoglobin	1/14 (7.1%)	2	0/15 (0%)	0	0/15 (0%)	0
Low Leukocytes	1/14 (7.1%)	3	0/15 (0%)	0	0/15 (0%)	0
Low Platelets	1/14 (7.1%)	3	0/15 (0%)	0	0/15 (0%)	0
SGOT (AST)	1/14 (7.1%)	4	0/15 (0%)	0	0/15 (0%)	0
SGPT (ALT)	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	7/14 (50%)	11	5/15 (33.3%)	6	3/15 (20%)	8
Bone pain	6/14 (42.9%)	6	3/15 (20%)	4	5/15 (33.3%)	7
Myalgia	6/14 (42.9%)	13	3/15 (20%)	3	3/15 (20%)	6
Pain - other	2/14 (14.3%)	2	3/15 (20%)	4	4/15 (26.7%)	8
Chest pain (non-cardiac and non-pleuritic)	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
Pelvic pain	0/14 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Arthritis	0/14 (0%)	0	1/15 (6.7%)	2	0/15 (0%)	0
Muscle weakness (not due to neuropathy)	0/14 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Nervous system disorders
Headache	0/14 (0%)	0	2/15 (13.3%)	2	1/15 (6.7%)	1
Neuropathy-sensory	4/14 (28.6%)	4	2/15 (13.3%)	2	2/15 (13.3%)	4
Mood alteration-depression	1/14 (7.1%)	3	0/15 (0%)	0	3/15 (20%)	3
Insomnia	1/14 (7.1%)	1	1/15 (6.7%)	1	1/15 (6.7%)	1
Neurology--other	1/14 (7.1%)	1	1/15 (6.7%)	1	1/15 (6.7%)	1
Syncope (fainting)	1/14 (7.1%)	2	1/15 (6.7%)	3	1/15 (6.7%)	1
Dizziness/Lightheadedness	0/14 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Memory Loss	0/14 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Vertigo	0/14 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Mood alteration-anxiety, agitation	1/14 (7.1%)	1	1/15 (6.7%)	1	1/15 (6.7%)	1
Renal and urinary disorders
Urinary frequency/urgency	2/14 (14.3%)	2	3/15 (20%)	4	1/15 (6.7%)	1
Creatinine	2/14 (14.3%)	3	1/15 (6.7%)	1	1/15 (6.7%)	1
Incontinence	1/14 (7.1%)	1	1/15 (6.7%)	1	0/15 (0%)	0
Renal/Genitourinary-Other	0/14 (0%)	0	1/15 (6.7%)	1	1/15 (6.7%)	1
Proteinuria	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
Hematuria	0/14 (0%)	0	2/15 (13.3%)	2	0/15 (0%)	0
Bladder hemorrhage	0/14 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Reproductive system and breast disorders
Gynecomastia	0/14 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Erectile impotence	1/14 (7.1%)	1	0/15 (0%)	0	0/15 (0%)	0
Libido	0/14 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/14 (7.1%)	1	2/15 (13.3%)	2	3/15 (20%)	3
Cough	0/14 (0%)	0	2/15 (13.3%)	2	3/15 (20%)	3
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other	2/14 (14.3%)	2	1/15 (6.7%)	1	2/15 (13.3%)	2
Injection site reaction	1/14 (7.1%)	1	0/15 (0%)	0	2/15 (13.3%)	3
Rash/desquamation	0/14 (0%)	0	1/15 (6.7%)	2	2/15 (13.3%)	2
Bruising (in absence of grade 3 or 4 thrombocytopenia)	1/14 (7.1%)	1	1/15 (6.7%)	1	0/15 (0%)	0
Flushing	0/14 (0%)	0	1/15 (6.7%)	1	1/15 (6.7%)	1
Pruritus	0/14 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0

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.