Sipuleucel-T With or Without Radiation Therapy in Treating Patients With Hormone-Resistant Metastatic Prostate Cancer

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01807065
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 51
• Locations: 3
• Arms: 2
• Duration (Months): 78.8
• Patients Per Site: 17
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well giving sipuleucel-T with or without radiation therapy works in treating patients with hormone-resistant metastatic prostate cancer. Vaccines may help the body build an effective immune response to kill tumor cells. Radiation therapy uses high energy x rays to kill tumor cells. It is not yet known whether giving sipuleucel-T vaccine is more effective with or without radiation therapy in treating prostate cancer

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate; Bone Metastases; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Soft Tissue Metastases; Stage IV Prostate Cancer	Biological: sipuleucel-T; Radiation: external beam radiation therapy; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the feasibility, based on percent able or willing to receive all three infusions of sipuleucel-T immunotherapy, when combining sipuleucel-T with radiation therapy to a single site of metastasis delivered one week prior to beginning of sipuleucel-T therapy.

SECONDARY OBJECTIVES:

1. To assess the effect of radiation therapy to single metastasis on immune response (antibody and T-cell proliferation to prostate acid phosphate [PAP] and fusion protein PA2024) generated by sipuleucel-T immunotherapy.

2. To assess the effect of external beam radiotherapy to single metastasis on prostate specific antigen (PSA) response to therapy with sipuleucel-T.

3. To assess the effect of external beam radiotherapy to single metastasis on radiographic response rate to therapy with sipuleucel-T.

4. To assess the time from the onset of therapy with sipuleucel-T +/- radiation to the need for subsequent therapy for prostate cancer.

5. To assess the toxicity associated with sipuleucel-T +/- radiation.

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

ARM A: Patients receive sipuleucel-T intravenously (IV) over 60 minutes days 22, 36, and 50.

ARM B: Patients undergo external beam radiation therapy in weeks 1-2. Patients also receive sipuleucel-T as in Arm A.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up until week 60.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Trial of Sipuleucel T Immunotherapy Preceded by Sensitizing Radiation Therapy and Sipuleucel-T Alone in Patients With Castrate Resistant Metastatic Prostate Cancer
• Study Start Date: Jun 7, 2013
• Actual Primary Completion Date: Dec 31, 2018
• Actual Study Completion Date: Dec 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (sipuleucel-T) Patients receive sipuleucel-T IV over 60 minutes days 22, 36, and 50.	Biological: sipuleucel-T; Given IV; Other Names: APC 8015 Provenge ; Other: laboratory biomarker analysis; Correlative studies
Experimental: Arm B (radiation therapy, sipuleucel-T) Patients undergo external beam radiation therapy in weeks 1-2. Patients also receive sipuleucel-T as in Arm A.	Biological: sipuleucel-T; Given IV; Other Names: APC 8015 Provenge ; Radiation: external beam radiation therapy; Undergo external beam radiation therapy; Other Names: EBRT ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [Until progression or death, Up to 2 years.]

   Estimated using the product-limit method of Kaplan and Meier. Progression is defined as one or more of the following: 20% increase in the sum of the longest diameters of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesions; PSA increase of 25% from baseline or nadir and by 2ng/uL or greater at 12 weeks; death due to disease without prior documentation of progression and without symptomatic deterioration.

Secondary Outcome Measures

1. Number of Participants With Grade 2 or Above Adverse Events [Up to 60 weeks]

   Number of participants with specified adverse event that is grade 2 or above and related to treatment. Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically documented adenocarcinoma of the prostate

• Life expectancy of >= 6 months, Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Metastatic disease as evidenced by soft tissue and/or bony metastases on baseline bone scan and/or computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen or pelvis

• Castration resistant prostatic adenocarcinoma; subjects must have current or historical evidence of disease progression despite castrated level of testosterone (< 50 ng/dL) achieved by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy; disease progression has to be demonstrated by PSA progression OR progression of measurable disease OR progression of non-measurable disease as defined below:

• PSA: Two consecutive rising PSA values, at least 7 days apart

• Measurable disease: >= 20% increase in the sum of the longest diameters of all measurable lesions or the development of any new lesions; the change will be measured against the best response to castration therapy or against the pre-castration measurements if there was no response

• Non-measurable disease:

• Soft tissue disease: The appearance of 1 or more lesions, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response

• Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression

• White blood cell (WBC) >= 2,500 cells/uL

• Absolute neutrophil count (ANC) >= 1,000 cells/uL

• Platelet count >= 75,000 cells/uL

• Hemoglobin (HgB) >= 9.0 g/dL

• Creatinine =< 2.5 mg/dL

• Total bilirubin =< 2 x institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST, serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT, serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN

• Prior chemotherapy with 0-2 regimens is allowed

• Prior radiation therapy to prostate or prostate bed is allowed provided it occurred > 3 months before enrollment to the study

Exclusion Criteria:

• The presence of liver, or known brain metastases, malignant pleural effusions, or malignant ascites

• Moderate or severe symptomatic metastatic disease, defined as a requirement for treatment with opioid analgesics for cancer-related pain within 21 days prior to registration

• Eastern Cooperative Oncology Group (ECOG) performance status > 2

• Treatment with chemotherapy within 3 months of registration

• Treatment with any of the following medications or interventions within 28 days of registration:

• Systematic corticosteroids; use of inhaled, intranasal, and topical steroids is acceptable

• Any other systemic therapy for prostate cancer (except for medical castration)

• History of external beam radiation therapy to metastatic sites within 1 year of enrollment to the study

• Participation in any previous study involving sipuleucel-T

• Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression

• Concurrent other malignancy with the exception of:

• Cutaneous squamous cell and basal carcinomas

• Adequately treated stage 1-2 malignancy

• Adequately treated stage 3-4 malignancy that has been in remission for >= 2 years at the time of registration

• A requirement for systemic immunosuppressive therapy for any reason

• Any infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5 degrees Fahrenheit [F] or 38.1 degrees Celsius [C]) within 1 week prior to registration

• Any medical intervention or other condition which, in the opinion of the principal investigator could compromise adherence with study requirements or otherwise compromise the study's objectives

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010
2	South Pasadena Cancer Center	Pasadena	California	United States	91030
3	Huntsman Cancer Institute, Univ. of Utah	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• City of Hope Medical Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Cy Stein, MD, PhD, City of Hope Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 24, 2017

More Information

Publications

None provided.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT01807065
• Other Study ID Numbers: 12367; NCI-2013-00542
• First Posted: Mar 8, 2013
• Last Update Posted: Aug 25, 2020
• Last Verified: Jun 1, 2019

• Additional relevant MeSH terms: Prostatic Neoplasms; Neoplasm Metastasis

Study Results

Participant Flow

Arm/Group Title	Arm A (Sipuleucel-T)	Arm B (Radiation Therapy, Sipuleucel-T)
Arm/Group Description	Patients receive sipuleucel-T IV over 60 minutes days 22, 36, and 50. Each dose of sipuleucel-T contains a minimum of 50 million activated CD54+ cells. sipuleucel-T: Given IV laboratory biomarker analysis: Correlative studies	Patients undergo external beam radiation therapy in weeks 1-2. Radiation given in 10 fractions of 300cGy for a total dose of 3000cGy. Patients also receive sipuleucel-T as in Arm A. sipuleucel-T: Given IV external beam radiation therapy: Undergo external beam radiation therapy laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	25	26
COMPLETED	24	25
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Arm A (Sipuleucel-T)	Arm B (Radiation Therapy, Sipuleucel-T)	Total
Arm/Group Description	Patients receive sipuleucel-T IV over 60 minutes days 22, 36, and 50. Each dose of sipuleucel-T contains a minimum of 50 million activated CD54+ cells. sipuleucel-T: Given IV laboratory biomarker analysis: Correlative studies	Patients undergo external beam radiation therapy in weeks 1-2. Radiation given in 10 fractions of 300cGy for a total dose of 3000cGy. Patients also receive sipuleucel-T as in Arm A. sipuleucel-T: Given IV external beam radiation therapy: Undergo external beam radiation therapy laboratory biomarker analysis: Correlative studies	Total of all reporting groups
Overall Participants	24	25	49
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64	67	67
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	24 100%	25 100%	49 100%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	20 83.3%	20 80%	40 81.6%
Hispanic	2 8.3%	2 8%	4 8.2%
Asian	0 0%	2 8%	2 4.1%
African American	2 8.3%	0 0%	2 4.1%
Not Reported	0 0%	1 4%	1 2%
Region of Enrollment (participants) [Number]
United States	24 100%	25 100%	49 100%
Gleason Score (Gleason grading) [Median (Full Range) ]
Median (Full Range) [Gleason grading]	8	7	8

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Estimated using the product-limit method of Kaplan and Meier. Progression is defined as one or more of the following: 20% increase in the sum of the longest diameters of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesions; PSA increase of 25% from baseline or nadir and by 2ng/uL or greater at 12 weeks; death due to disease without prior documentation of progression and without symptomatic deterioration.
Time Frame	Until progression or death, Up to 2 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Sipuleucel-T)	Arm B (Radiation Therapy, Sipuleucel-T)
Arm/Group Description	Patients receive sipuleucel-T IV over 60 minutes days 22, 36, and 50. Each dose of sipuleucel-T contains a minimum of 50 million activated CD54+ cells. sipuleucel-T: Given IV laboratory biomarker analysis: Correlative studies	Patients undergo external beam radiation therapy in weeks 1-2. Radiation given in 10 fractions of 300cGy for a total dose of 3000cGy. Patients also receive sipuleucel-T as in Arm A. sipuleucel-T: Given IV external beam radiation therapy: Undergo external beam radiation therapy laboratory biomarker analysis: Correlative studies
Measure Participants	24	25
Median (95% Confidence Interval) [Months]	2.46	3.65

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Sipuleucel-T), Arm B (Radiation Therapy, Sipuleucel-T)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Number of Participants With Grade 2 or Above Adverse Events
Description	Number of participants with specified adverse event that is grade 2 or above and related to treatment. Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Time Frame	Up to 60 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Sipuleucel-T)	Arm B (Radiation Therapy, Sipuleucel-T)
Arm/Group Description	Patients receive sipuleucel-T IV over 60 minutes days 22, 36, and 50. Each dose of sipuleucel-T contains a minimum of 50 million activated CD54+ cells. sipuleucel-T: Given IV laboratory biomarker analysis: Correlative studies	Patients undergo external beam radiation therapy in weeks 1-2. Radiation given in 10 fractions of 300cGy for a total dose of 3000cGy. Patients also receive sipuleucel-T as in Arm A. sipuleucel-T: Given IV external beam radiation therapy: Undergo external beam radiation therapy laboratory biomarker analysis: Correlative studies
Measure Participants	24	25
Grade 2 : Chills	3 12.5%	0 0%
Grade 2 : Fatigue	1 4.2%	2 8%
Grade 2 : Infusion Reaction	1 4.2%	1 4%
Grade 2 : Decreased Lymphocyte Count	1 4.2%	0 0%
Grade 2 : Nausea	0 0%	1 4%
Grade 2 : Pain in Extremity	0 0%	1 4%
Grade 2 : Anemia	0 0%	1 4%
Grade 2 : Anorexia	0 0%	1 4%
Grade 2 : Headache	1 4.2%	1 4%
Grade 2 : Hypertension	0 0%	3 12%
Grade 3 : Chills	0 0%	0 0%
Grade 3 : Fatigue	0 0%	0 0%
Grade 3 : Infusion Reaction	0 0%	0 0%
Grade 3 : Decreased Lymphocyte Count	0 0%	0 0%
Grade 3 : Nausea	0 0%	0 0%
Grade 3 : Pain in Extremity	0 0%	0 0%
Grade 3 : Anemia	0 0%	1 4%
Grade 3 : Anorexia	0 0%	0 0%
Grade 3 : Headache	0 0%	0 0%
Grade 3 : Hypertension	0 0%	0 0%

Adverse Events

Time Frame	Adverse events were collected over a period of 1 year and 3 months.
Adverse Event Reporting Description	"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Arm/Group Title	Arm A (Sipuleucel-T)		Arm B (Radiation Therapy, Sipuleucel-T)
Arm/Group Description	Patients receive sipuleucel-T IV over 60 minutes days 22, 36, and 50. Each dose of sipuleucel-T contains a minimum of 50 million activated CD54+ cells. sipuleucel-T: Given IV laboratory biomarker analysis: Correlative studies		Patients undergo external beam radiation therapy in weeks 1-2. Radiation given in 10 fractions of 300cGy for a total dose of 3000cGy. Patients also receive sipuleucel-T as in Arm A. sipuleucel-T: Given IV external beam radiation therapy: Undergo external beam radiation therapy laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Arm A (Sipuleucel-T)		Arm B (Radiation Therapy, Sipuleucel-T)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/24 (0%)
Serious Adverse Events
	Arm A (Sipuleucel-T)		Arm B (Radiation Therapy, Sipuleucel-T)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/25 (4%)		1/24 (4.2%)
Infections and infestations
Skin infection	1/25 (4%)	1	0/24 (0%)	0
Renal and urinary disorders
Hematuria	0/25 (0%)	0	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	Arm A (Sipuleucel-T)		Arm B (Radiation Therapy, Sipuleucel-T)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/25 (100%)		24/24 (100%)
Blood and lymphatic system disorders
Anemia	7/25 (28%)	20	11/24 (45.8%)	34
Leukocytosis	0/25 (0%)	0	1/24 (4.2%)	3
Cardiac disorders
Sinus bradycardia	7/25 (28%)	19	7/24 (29.2%)	18
Sinus tachycardia	3/25 (12%)	3	0/24 (0%)	0
Eye disorders
Watering eyes	1/25 (4%)	1	0/24 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/25 (4%)	1	3/24 (12.5%)	4
Constipation	0/25 (0%)	0	5/24 (20.8%)	9
Diarrhea	1/25 (4%)	1	2/24 (8.3%)	3
Dyspepsia	1/25 (4%)	1	1/24 (4.2%)	1
Esophagitis	0/25 (0%)	0	2/24 (8.3%)	2
Gastritis	0/25 (0%)	0	1/24 (4.2%)	1
Gastroesophageal reflux disease	1/25 (4%)	3	3/24 (12.5%)	3
Gastrointestinal pain	0/25 (0%)	0	1/24 (4.2%)	1
Lower gastrointestinal hemorrhage	0/25 (0%)	0	1/24 (4.2%)	1
Nausea	2/25 (8%)	3	7/24 (29.2%)	13
Oral dysesthesia	1/25 (4%)	1	0/24 (0%)	0
Vomiting	3/25 (12%)	3	4/24 (16.7%)	5
Angioectasia	0/25 (0%)	0	1/24 (4.2%)	1
dry heaves	0/25 (0%)	0	1/24 (4.2%)	1
General disorders
Chills	9/25 (36%)	17	2/24 (8.3%)	2
Fatigue	12/25 (48%)	22	10/24 (41.7%)	19
Fever	2/25 (8%)	2	1/24 (4.2%)	1
Flu like symptoms	1/25 (4%)	1	2/24 (8.3%)	2
Infusion related reaction	2/25 (8%)	2	2/24 (8.3%)	3
Pain	3/25 (12%)	4	4/24 (16.7%)	9
Immune system disorders
Allergic reaction	1/25 (4%)	1	0/24 (0%)	0
Infections and infestations
Bronchial infection	0/25 (0%)	0	1/24 (4.2%)	1
apheresis line infection	0/25 (0%)	0	2/24 (8.3%)	4
Injury, poisoning and procedural complications
Bruising	1/25 (4%)	2	1/24 (4.2%)	1
Dermatitis radiation	1/25 (4%)	1	4/24 (16.7%)	10
Fall	2/25 (8%)	2	1/24 (4.2%)	1
Fracture	1/25 (4%)	1	0/24 (0%)	0
Vascular access complication	1/25 (4%)	1	0/24 (0%)	0
Investigations
Alanine aminotransferase increased	1/25 (4%)	2	1/24 (4.2%)	1
Alkaline phosphatase increased	4/25 (16%)	11	7/24 (29.2%)	15
Aspartate aminotransferase increased	3/25 (12%)	5	4/24 (16.7%)	7
Blood bilirubin increased	0/25 (0%)	0	2/24 (8.3%)	2
Creatinine increased	2/25 (8%)	3	2/24 (8.3%)	6
Lymphocyte count decreased	1/25 (4%)	1	1/24 (4.2%)	3
Neutrophil count decreased	2/25 (8%)	5	1/24 (4.2%)	2
Platelet count decreased	3/25 (12%)	5	7/24 (29.2%)	20
Weight loss	1/25 (4%)	3	1/24 (4.2%)	1
White blood cell decreased	4/25 (16%)	7	3/24 (12.5%)	7
Metabolism and nutrition disorders
Anorexia	1/25 (4%)	1	4/24 (16.7%)	7
Hypercalcemia	0/25 (0%)	0	1/24 (4.2%)	1
Hyperkalemia	1/25 (4%)	1	1/24 (4.2%)	4
Hypernatremia	4/25 (16%)	5	2/24 (8.3%)	2
Hypertriglyceridemia	1/25 (4%)	1	0/24 (0%)	0
Hypoalbuminemia	0/25 (0%)	0	3/24 (12.5%)	4
Hypocalcemia	2/25 (8%)	4	0/24 (0%)	0
Hypoglycemia	2/25 (8%)	2	1/24 (4.2%)	4
Hypokalemia	0/25 (0%)	0	1/24 (4.2%)	1
Hyponatremia	1/25 (4%)	1	4/24 (16.7%)	9
Hypophosphatemia	1/25 (4%)	2	2/24 (8.3%)	6
Obesity	1/25 (4%)	2	1/24 (4.2%)	4
Musculoskeletal and connective tissue disorders
Arthritis	0/25 (0%)	0	1/24 (4.2%)	1
Back pain	3/25 (12%)	4	6/24 (25%)	9
Bone pain	3/25 (12%)	4	0/24 (0%)	0
Chest wall pain	1/25 (4%)	2	0/24 (0%)	0
Flank pain	0/25 (0%)	0	1/24 (4.2%)	1
Myalgia	0/25 (0%)	0	1/24 (4.2%)	1
Neck pain	0/25 (0%)	0	2/24 (8.3%)	2
Pain in extremity	3/25 (12%)	5	6/24 (25%)	10
neck stiffness	0/25 (0%)	0	1/24 (4.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
enlarged thryroid nodule	1/25 (4%)	1	0/24 (0%)	0
skin lesion	0/25 (0%)	0	1/24 (4.2%)	3
skin lesion - neoplasm benign	0/25 (0%)	0	1/24 (4.2%)	1
Nervous system disorders
Dizziness	2/25 (8%)	4	2/24 (8.3%)	2
Facial muscle weakness	0/25 (0%)	0	2/24 (8.3%)	6
Headache	3/25 (12%)	5	2/24 (8.3%)	5
Paresthesia	1/25 (4%)	4	3/24 (12.5%)	7
Radiculitis	0/25 (0%)	0	1/24 (4.2%)	1
Tingling face, hands, and feet	1/25 (4%)	1	0/24 (0%)	0
generalized numbness and tingling during	1/25 (4%)	1	0/24 (0%)	0
numbness and tingling in right hand	1/25 (4%)	2	0/24 (0%)	0
Psychiatric disorders
Insomnia	2/25 (8%)	2	1/24 (4.2%)	1
Renal and urinary disorders
Hematuria	1/25 (4%)	1	1/24 (4.2%)	1
Proteinuria	0/25 (0%)	0	1/24 (4.2%)	1
Urinary frequency	0/25 (0%)	0	2/24 (8.3%)	4
Urinary incontinence	2/25 (8%)	2	0/24 (0%)	0
decreased force of urinary stream	0/25 (0%)	0	1/24 (4.2%)	3
Reproductive system and breast disorders
Erectile dysfunction	1/25 (4%)	1	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/25 (4%)	1	2/24 (8.3%)	4
Dyspnea	0/25 (0%)	0	1/24 (4.2%)	1
Hoarseness	1/25 (4%)	2	0/24 (0%)	0
Nasal congestion	1/25 (4%)	2	0/24 (0%)	0
Postnasal drip	1/25 (4%)	1	0/24 (0%)	0
Sore throat	0/25 (0%)	0	1/24 (4.2%)	1
Skin and subcutaneous tissue disorders
'mild skin irritation in the posterior r	0/25 (0%)	0	1/24 (4.2%)	1
Alopecia	0/25 (0%)	0	1/24 (4.2%)	4
Periorbital edema	0/25 (0%)	0	1/24 (4.2%)	1
Scalp pain	0/25 (0%)	0	1/24 (4.2%)	1
contact dermatitis	0/25 (0%)	0	1/24 (4.2%)	1
Vascular disorders
Hot flashes	0/25 (0%)	0	1/24 (4.2%)	1
Hypertension	11/25 (44%)	33	12/24 (50%)	35
Hypotension	2/25 (8%)	4	2/24 (8.3%)	3

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.