Effect of Flutamide on Biomarkers in Blood and Tissue Samples From Patients at High Risk of Ovarian Cancer

• Sponsor: University of Arizona (Other)
• Overall Status: Completed
• CT.gov ID: NCT00699907
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 127
• Location: 1
• Arms: 3
• Duration (Months): 118
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

Studying samples of blood and tissue in the laboratory from patients with a high risk of developing ovarian cancer may help doctors identify and learn more about biomarkers related to cancer. We hypothesized that (i) preclinical biologic evidence exists for the role of androgens in ovarian cancer development and (ii) flutamide treatment of women at high risk for ovarian cancer may identify meaningful tissue biomarkers of androgen action and of ovarian cancer initiation. This phase II trial studied the effect of flutamide on biomarkers in blood and tissue samples from patients at high risk of ovarian cancer.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: flutamide	Phase 2

Detailed Description

OBJECTIVE: Compare the biomarkers of patients at high risk for ovarian cancer who are undergoing prophylactic oophorectomy and are interested in taking flutamide vs patients at high risk for ovarian cancer who are undergoing prophylactic oophorectomy and are not interested in taking flutamide (control) vs patients who are undergoing oophorectomy for a medical indication (control).

OUTLINE: Patients who elected not to receive flutamide received prophylactic oophorectomy or oophorectomy for a medical indication. Patients who elected to receive flutamide received 125mg once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent prophylactic oophorectomy. All patients underwent blood and ovarian tissue sample collection at the time of surgery for biomarker laboratory studies. Proteomic, microarray, and polymorphism analysis were performed on the blood and tissue samples.

Study Design

• Study Type: Interventional
• Actual Enrollment: 127 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Prospective, Phase IIA Study of the Effect of Flutamide (125 MG/DAY) Taken for 6 Weeks on Expression of Potential Biomarkers of Flutamide Action in the Ovaries of Women at Increased Risk for Ovarian Cancer
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment Arm Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	Drug: flutamide; Patients receive oral flutamide (125 MG/DAY) once daily for 6 weeks in the absence of unacceptable toxicity.; Other Names: Eulexin Cytomid Cebatrol Chimax Drogenil Flucinom Flutamin Fugerel Niftolide Sebatrol
No Intervention: High Risk Arm High risk patients underwent risk-reducing salpingo-oophorectomy.
No Intervention: Low Risk Arm Low risk patients underwent salpingo-oophorectomy for a medical indication.

Outcome Measures

Primary Outcome Measures

1. Colony Stimulating Factor (CSF-1) Expression in Ovarian Endosalpingiosis [Surgery]

   CSF-1 levels were measured by immunohistochemistry (IHC). The modified H-Score assess extent of nuclear immunoreactivity applicable to steroid receptors. The modified H-scores total range is 0-300. A lower modified H-score indicates weakly staining nuclei. A higher modified H-score indicated strongly staining nuclei. This applies to all measures.

2. Colony Stimulating Factor (CSF-1) Expression in Ovarian Epithelium [Surgery]

   CSF-1 levels were measured by immunohistochemistry (IHC).

3. Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma [Surgery]

   CSF-1 levels were measured by immunohistochemistry (IHC).

4. Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis [Surgery]

   CSF-1R levels were measured by immunohistochemistry (IHC).

5. Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium [Surgery]

   CSF-1R levels were measured by immunohistochemistry (IHC).

6. Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma [Surgery]

   CSF-1R levels were measured by immunohistochemistry (IHC).

7. Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis [Surgery]

   ErbB4 levels were measured by immunohistochemistry (IHC).

8. Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium [Surgery]

   ErbB4 levels were measured by immunohistochemistry (IHC).

9. Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma [Surgery]

   ErbB4 levels were measured by immunohistochemistry (IHC).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 83 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria for all patients:

• ≥ 18 years of age

• Able to comply with study and follow-up requirements

Inclusion Criteria for high risk patients:

• elected to undergo prophylactic salpingo-oophorectomy

• fertile patients must use effective non-hormonal contraception

• agreed to use a nonhormonal means of contraception before surgery

• serum bilirubin ≤ 1.0 x Upper Limit Normal (ULN), alkaline phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) ≤ 2.5 x ULN

• serum creatinine ≤ 1.5 x ULN

• granulocyte count ≥ 1500/μL

• platelet count ≥ 75,000/μL

• hemoglobin ≥ 9 g/dL

• adequate complete blood count

• At high risk for developing ovarian cancer, as defined by any of the following:

• Breast Cancer carried a BRCA1 or BRCA2 deleterious mutation, a Lynch syndrome mutation, and/or defined by a family history of: 1 first-degree relative with epithelial ovarian cancer, ≥1 first-degree female relative with breast cancer when ≤40 years old, ≥1 first-degree female relative with breast cancer when ≤50 years old, male relative with breast cancer, and/or family history of breast cancer or ovarian cancer.

Inclusion Criteria for low risk patients:

• planning to undergo oophorectomy for a medical indication

• did not fulfill criteria for high risk of developing ovarian cancer

Exclusion criteria:

• liver disease, current alcohol abuse, or cirrhosis

• pregnancy or lactation

• current use of hormone therapy

• active treatment for cancer

• recent, current, or planned participation in another experimental drug study

• breast cancer within the past 5 years

• significant traumatic injury within the past 6 months

• major surgery within the past 6 months

• any disease, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates the continued use of an investigational drug or that may render the patient at high risk from treatment complication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States	85724-5024

Sponsors and Collaborators

• University of Arizona
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Setsuko K. Chambers, MD, University of Arizona Arizona Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• American Journal of Cancer Research, 2014.

Publications

None provided.

• Responsible Party: University of Arizona
• ClinicalTrials.gov Identifier: NCT00699907
• Other Study ID Numbers: 04-0707-04; P30CA023074
• First Posted: Jun 18, 2008
• Last Update Posted: Jul 24, 2018
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Arizona: Ovarian epithelial cancer; High risk; Biomarkers
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Flutamide

Study Results

Participant Flow

Recruitment Details	Participants were recruited from the medical clinic prior to oophorectomy. Participants were recruited from January 2007 until June 2011.
Pre-assignment Detail	Participants were assigned to groups immediately after being enrolled.

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.
Period Title: Overall Study
STARTED	14	57	56
COMPLETED	12	47	48
NOT COMPLETED	2	10	8

Baseline Characteristics

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm	Total
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy. flutamide: Patients receive oral flutamide (125 MG/DAY) once daily for 6 weeks in the absence of unacceptable toxicity.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.	Total of all reporting groups
Overall Participants	12	47	48	107
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	45.2	46.9	51.7	48.9
Sex: Female, Male (Count of Participants)
Female	12 100%	47 100%	48 100%	107 100%
Male	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	47 100%	48 100%	107 100%

Outcome Measures

1. Primary Outcome

Title	Colony Stimulating Factor (CSF-1) Expression in Ovarian Endosalpingiosis
Description	CSF-1 levels were measured by immunohistochemistry (IHC). The modified H-Score assess extent of nuclear immunoreactivity applicable to steroid receptors. The modified H-scores total range is 0-300. A lower modified H-score indicates weakly staining nuclei. A higher modified H-score indicated strongly staining nuclei. This applies to all measures.
Time Frame	Surgery

Outcome Measure Data

Analysis Population Description

The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.
Measure Participants	7	24	15
Median (Full Range) [Modified H-Score]	5	130	50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Arm, High Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Risk Arm, Low Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

2. Primary Outcome

Title	Colony Stimulating Factor (CSF-1) Expression in Ovarian Epithelium
Description	CSF-1 levels were measured by immunohistochemistry (IHC).
Time Frame	Surgery

Outcome Measure Data

Analysis Population Description

The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.
Measure Participants	8	42	39
Median (Full Range) [Histo-score (H-Score)]	0	50	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Arm, High Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Risk Arm, Low Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

3. Primary Outcome

Title	Colony Stimulating Factor (CSF-1) Expression in Ovarian Stroma
Description	CSF-1 levels were measured by immunohistochemistry (IHC).
Time Frame	Surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.
Measure Participants	11	45	43
Median (Full Range) [Histo-score (H-Score)]	5	40	35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Arm, High Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Risk Arm, Low Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

4. Primary Outcome

Title	Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Endosalpingiosis
Description	CSF-1R levels were measured by immunohistochemistry (IHC).
Time Frame	Surgery

Outcome Measure Data

Analysis Population Description

The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.
Measure Participants	6	21	16
Median (Full Range) [Histo-score (H-Score)]	15	160	75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Arm, High Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Risk Arm, Low Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

5. Primary Outcome

Title	Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Epithelium
Description	CSF-1R levels were measured by immunohistochemistry (IHC).
Time Frame	Surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.
Measure Participants	12	41	36
Median (Full Range) [Histo-score (H-Score)]	0	40	20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Arm, High Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Risk Arm, Low Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

6. Primary Outcome

Title	Colony Stimulating Factor-1 Receptor (CSF-1R) Expression in Ovarian Stroma
Description	CSF-1R levels were measured by immunohistochemistry (IHC).
Time Frame	Surgery

Outcome Measure Data

Analysis Population Description

The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.
Measure Participants	12	42	42
Median (Full Range) [Histo-score (H-Score)]	20	40	53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Arm, High Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Risk Arm, Low Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

7. Primary Outcome

Title	Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Endosalpingiosis
Description	ErbB4 levels were measured by immunohistochemistry (IHC).
Time Frame	Surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.
Measure Participants	7	19	9
Median (Full Range) [Histo-score (H-Score)]	5	60	10

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Arm, High Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Risk Arm, Low Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

8. Primary Outcome

Title	Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Epithelium
Description	ErbB4 levels were measured by immunohistochemistry (IHC).
Time Frame	Surgery

Outcome Measure Data

Analysis Population Description

The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.
Measure Participants	8	33	20
Median (Full Range) [Histo-score (H-Score)]	0	55	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Arm, High Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Risk Arm, Low Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

9. Primary Outcome

Title	Tyrosine Kinase V-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog-4 (ErbB4) Expression in Ovarian Stroma
Description	ErbB4 levels were measured by immunohistochemistry (IHC).
Time Frame	Surgery

Outcome Measure Data

Analysis Population Description

The Overall Number of Participants Analyzed represents all participants with a modified Histo-score that could be evaluated

Arm/Group Title	Treatment Arm	High Risk Arm	Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.	High risk patients underwent risk-reducing salpingo-oophorectomy.	Low risk patients underwent salpingo-oophorectomy for a medical indication.
Measure Participants	11	36	23
Median (Full Range) [Histo-score (H-Score)]	10	90	30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Arm, High Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Risk Arm, Low Risk Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Adverse Events

Arm/Group Title	Treatment Arm		High Risk Arm		Low Risk Arm
Arm/Group Description	Patients received oral flutamide (125 MG) once daily for 6 weeks in the absence of unacceptable toxicity. Patients then underwent risk-reducing salpingo-oophorectomy.		High risk patients underwent risk-reducing salpingo-oophorectomy.		Low risk patients underwent salpingo-oophorectomy for a medical indication.
All Cause Mortality
	Treatment Arm		High Risk Arm		Low Risk Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment Arm		High Risk Arm		Low Risk Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/47 (0%)		0/48 (0%)
Other (Not Including Serious) Adverse Events
	Treatment Arm		High Risk Arm		Low Risk Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/12 (75%)		0/47 (0%)		0/48 (0%)
Blood and lymphatic system disorders
Hemoglobin	1/12 (8.3%)	1	0/47 (0%)	0	0/48 (0%)	0
Hyponatremia	1/12 (8.3%)	1	0/47 (0%)	0	0/48 (0%)	0
Endocrine disorders
Endocrine	1/12 (8.3%)	1	0/47 (0%)	0	0/48 (0%)	0
Gastrointestinal disorders
Constipation	1/12 (8.3%)	1	0/47 (0%)	0	0/48 (0%)	0
Diarrhea	1/12 (8.3%)	1	0/47 (0%)	0	0/48 (0%)	0
Nausea	2/12 (16.7%)	2	0/47 (0%)	0	0/48 (0%)	0
General disorders
Hot flashes	1/12 (8.3%)	1	0/47 (0%)	0	0/48 (0%)	0
Pain - Other	1/12 (8.3%)	1	0/47 (0%)	0	0/48 (0%)	0
Pain - Head/headache	2/12 (16.7%)	2	0/47 (0%)	0	0/48 (0%)	0
Musculoskeletal and connective tissue disorders
Pain - Muscle	1/12 (8.3%)	1	0/47 (0%)	0	0/48 (0%)	0
Musculoskeletal/Soft Tissue - other	1/12 (8.3%)	2	0/47 (0%)	0	0/48 (0%)	0
Renal and urinary disorders
Urinary frequency/urgency	1/12 (8.3%)	1	0/47 (0%)	0	0/48 (0%)	0
Urine color change	3/12 (25%)	3	0/47 (0%)	0	0/48 (0%)	0
Skin and subcutaneous tissue disorders
Burn	1/12 (8.3%)	1	0/47 (0%)	0	0/48 (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.