Lapatinib Ditosylate in Treating Patients With Ductal Breast Carcinoma In Situ

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00555152
• Collaborator: (none)
• Enrollment: 22
• Locations: 2
• Arms: 2
• Actual Duration (Months): 60.3
• Patients Per Site: 11
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This randomized phase I/II trial studies the side effects and best dose of lapatinib ditosylate and to see how well it works in treating patients with ductal breast carcinoma in situ. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Ductal Breast Carcinoma In Situ; HER2/Neu Positive	Other: Laboratory Biomarker Analysis; Drug: Lapatinib Ditosylate; Other: Placebo	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. Determine whether lapatinib (lapatinib ditosylate) therapy at the dose of 1000 mg results in a statistically significantly lower rate of proliferation in ductal carcinoma in situ (DCIS) breast cancer cells as measured by Ki67 when compared to placebo.

2. Determine the toxicity profile and frequency of adverse events in women with DCIS breast cancer taking lapatinib at 1000 mg as compared to women taking placebo.

SECONDARY OBJECTIVES:

1. Determine whether lapatinib treatment affects the incidence of DCIS seen at the time of surgical excision.

2. Determine whether treatment with lapatinib will modulate breast tissue histology or the expression of specific biomarkers in normal and DCIS breast cancer cells.

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

ARM I: Patients receive lapatinib ditosylate orally (PO) once daily (QD) for 2-6 weeks until the time of surgery.

ARM II: Patients receive placebo PO QD for 2-6 weeks until the time of surgery.

After completion of study treatment, patients are followed for 4-5 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Neoadjuvant Trial of Lapatinib for the Treatment of Women With DCIS Breast Cancer
• Actual Study Start Date: Aug 19, 2009
• Actual Primary Completion Date: Aug 28, 2014
• Actual Study Completion Date: Aug 28, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (lapatinib ditosylate) Patients receive lapatinib ditosylate PO once QD for 2-6 weeks until the time of surgery.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lapatinib Ditosylate; Given PO; Other Names: Tykerb
Placebo Comparator: Arm II (placebo) Patients receive placebo PO QD for 2-6 weeks until the time of surgery.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo; Given PO; Other Names: placebo therapy PLCB sham therapy

Outcome Measures

Primary Outcome Measures

1. Proliferation (Ki67 IHC) in Ductal Breast Carcinoma In Situ (DCIS) [2-6 weeks from baseline to surgery, up to 6 weeks]

   Reduction in percent of Ki67 positive cells at surgery compared to baseline as a function of treatment. Analysis of the primary treatment comparison will be based on a two sample t-test comparing change in log-transformed Ki67% for placebo and treated subjects. P-values of 0.05 will be considered significant. Proliferation will be assessed by immunohistochemical (IHC) staining for Ki67, and the change in percentage of Ki67 positive cells will be compared in lapatinib-treated samples versus placebo.

2. Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0 [From baseline to 4-5 weeks after surgery]

   Toxicity profile summarized reflects incidence by number of participants affected with adverse events by Maximum Grade 1 to 3, additional adverse event according to the NCI CTCAE version 3.0 reported in Adverse Event section results.

Secondary Outcome Measures

1. Incidence of Ductal Carcinoma in Situ Remaining at Resection [2-6 weeks from baseline to surgery, up to 6 weeks]

   Number of participants with DCIS incidence on surgical excision. Differences in histologic response (disappearance of DCIS) will be evaluated using Fisher's exact test. Correlation analysis and linear models will be used to evaluate associations among marker values at baseline and among changes in marker values and treatment. All statistical tests will be two-sided.

2. Biomarker Analysis of Proliferation Markers [2-6 weeks from baseline to surgery, Up to 6 weeks]

   Correlation analysis and linear models will be used to evaluate associations among marker values at baseline and among changes in marker values and treatment. All statistical tests will be two-sided.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must be premenopausal or postmenopausal

• Participants must have a diagnosis of ductal carcinoma in situ made by core needle biopsy

• The DCIS cells must have high expression of human epidermal growth factor receptor 2 (erbB2) (3+ by immunohistochemical staining or amplification by fluorescence in situ hybridization [FISH]), and/or have detectable expression of epidermal growth factor receptor (EGFR) (1+ or more by immunohistochemical staining)

• All participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• Individuals with a diagnosis of breast cancer, non-melanoma skin cancer, cervical cancer in situ, or early bladder cancer are eligible if they have not been treated with chemotherapy, biological therapy, or breast radiotherapy to the breast currently affected by DCIS within one year; in addition, individuals with a diagnosis of breast cancer may not have used tamoxifen, raloxifene, or other antiestrogen compounds within three months of study day 1

• If subjects are of reproductive potential, they must agree to use a reliable contraceptive method or be sexually abstinent; subjects must fulfill these conditions beginning at the time of starting study medications and ending one month after study termination

• Negative serum pregnancy test (beta-human chorionic gonadotropin [HCG]) at baseline (within 30 days of day 0) for women of child bearing potential

• Serum creatinine =< 1.5 times the institution?s upper limit of normal

• Total bilirubin =< 1.5 times the institution's upper limits of normal

• Serum glutamic oxaloacetic transaminase (SGOT) =< 1.5 times the institution's upper limits of normal

• Alkaline phosphatase =< 1.5 times the institution's upper limits of normal

• Albumin =< 1.5 times the institution's upper limits of normal

• White blood cells (WBC) > 4.0 k/uL

• Platelet count > 100,000/uL

• Hematocrit of > 30%

• Cardiac ejection fraction within normal limits for the institution by multi gated acquisition scan (MUGA) scan or normal cardiac ultrasound (defined as within the upper limit of normal [ULN] for the institution)

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Willingness to refrain from donating blood to others during the study

Exclusion Criteria:

• Individuals are ineligible if they have either active cancer or a prior history of malignancies other than (e.g., breast cancer, skin cancer [basal or squamous cell carcinoma], cervical cancer in situ, or early bladder cancer [preinvasive transitional cell carcinoma of the bladder]) within the past five years

• Participants are ineligible if they are currently being treated with tamoxifen, raloxifene, or with aromatase inhibitors (letrozole, anastrozole, exemestane)

• Individuals are ineligible if they have received chemotherapy, biological therapy (e.g., Herceptin), or radiotherapy for the treatment of any cancer within 1 year or if they have received tamoxifen, raloxifene, letrozole, anastrozole, or exemestane therapy within 3 months of study day 1

• Individuals currently receiving anticoagulation therapy (e.g., Coumadin) are ineligible

• Blood urea nitrogen [BUN] > 1.5 x ULN or

• Creatinine [Cr] > 1.5 x ULN

• SGOT > 1.5 x ULN

• Serum glutamate pyruvate transaminase (SGPT) > 1.5 x ULN

• Alkaline phosphatase > 1.5 x ULN

• Bilirubin > 1.5x ULN

• Individuals who are currently participating in a study of an investigational drug

• Pregnancy, lactation or unwillingness to use a reliable contraceptive method in women of childbearing potential

• Severe underlying chronic illness or disease, such as uncontrolled diabetes

• Individuals with known congestive heart disease or previous myocardial infarction are ineligible

• Patients taking any prohibited medications

• Individuals with hypokalemia or hypomagnesemia are ineligible unless these conditions are corrected to within normal limits before starting drug

• Individuals with congenital long QT syndrome or baseline QTcF intervals > 480 msec on electrocardiogram (EKG)

• Individuals taking anti-arrhythmics, beta blockers, or other medications that may lead to QT prolongation

• Individuals who have received a cumulative dose of anthracycline therapy greater than 500 mg/m^2 are ineligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Powel Brown, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00555152
• Other Study ID Numbers: NCI-2009-00875; NCI-2009-00875; 2008-0086; CDR0000573719; H-19895; P50CA058183; P30CA016672; NCT00570453
• First Posted: Nov 7, 2007
• Last Update Posted: Apr 20, 2018
• Last Verified: Mar 1, 2018

• Additional relevant MeSH terms: Carcinoma; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Breast Carcinoma In Situ; Carcinoma, Intraductal, Noninfiltrating; Lapatinib

Study Results

Participant Flow

Recruitment Details	Activated 1/17/2008 at Baylor College of Medicine (BCM), MD Anderson Cancer Center, Dana-Farber Cancer Institute, Mayo Clinic, Georgetown University & Walter Reed Army Medical Center; closed at BCM 3/8/2010, re-activated 9/19/2011 at MD Anderson, Dana-Farber Cancer Institute, Mayo Clinic & University of Alabama, Birmingham, closed 8/28/2014.
Pre-assignment Detail	A total of 22 participants were enrolled and randomized to 3 of 4 treatment arms; Two of the 4 initial arms were removed in the second period with one of those having no enrollment. Three participants were enrolled while the study was open at BCM, the other 19 were enrolled after the study was transferred to MD Anderson (second study period).

Arm/Group Title	Arm I Lapatinib 1500 mg	Arm II Lapatinib 1000 mg	Arm III Lapatinib 750 mg	Arm IV Placebo
Arm/Group Description	Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.	Placebo orally once daily for 2-6 weeks until the time of surgery.
Period Title: Period Open at BCM: 1/17/08-3/8/10
STARTED	2	0	0	1
COMPLETED	2	0	0	1
NOT COMPLETED	0	0	0	0
Period Title: Period Open at BCM: 1/17/08-3/8/10
STARTED	0	10	0	9
COMPLETED	0	10	0	9
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Arm I Lapatinib 1500 mg	Arm II Lapatinib 1000 mg	Arm III Lapatinib 750 mg	Arm IV Placebo	Total
Arm/Group Description	Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.	Placebo orally once daily for 2-6 weeks until the time of surgery.	Total of all reporting groups
Overall Participants	2	10	0	10	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46 (9.5)	51.7 (10.7)	52 (8.4)	51.3 (9.3)
Sex: Female, Male (Count of Participants)
Female	2 100%	10 100%	10 Infinity	22 220%
Male	0 0%	0 0%	0 NaN	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 10%	2 Infinity	3 30%
Not Hispanic or Latino	2 100%	9 90%	8 Infinity	19 190%
Unknown or Not Reported	0 0%	0 0%	0 NaN	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 NaN	0 0%
Asian	0 0%	1 10%	0 NaN	1 10%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 NaN	0 0%
Black or African American	0 0%	0 0%	0 NaN	0 0%
White	2 100%	9 90%	9 Infinity	20 200%
More than one race	0 0%	0 0%	0 NaN	0 0%
Unknown or Not Reported	0 0%	0 0%	1 Infinity	1 10%
Region of Enrollment (participants) [Number]
United States	2 100%	10 100%	10 Infinity	22 220%

Outcome Measures

1. Primary Outcome

Title	Proliferation (Ki67 IHC) in Ductal Breast Carcinoma In Situ (DCIS)
Description	Reduction in percent of Ki67 positive cells at surgery compared to baseline as a function of treatment. Analysis of the primary treatment comparison will be based on a two sample t-test comparing change in log-transformed Ki67% for placebo and treated subjects. P-values of 0.05 will be considered significant. Proliferation will be assessed by immunohistochemical (IHC) staining for Ki67, and the change in percentage of Ki67 positive cells will be compared in lapatinib-treated samples versus placebo.
Time Frame	2-6 weeks from baseline to surgery, up to 6 weeks

Outcome Measure Data

Analysis Population Description

No outcome data available due to laboratory issues affecting the analysis of biomarkers results.

Arm/Group Title	Arm I Lapatinib 1500 mg	Arm II Lapatinib 1000 mg	Arm III Lapatinib 750 mg	Arm IV Placebo
Arm/Group Description	Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.	Placebo orally once daily for 2-6 weeks until the time of surgery.
Measure Participants	0	0	0	0

2. Secondary Outcome

Title	Incidence of Ductal Carcinoma in Situ Remaining at Resection
Description	Number of participants with DCIS incidence on surgical excision. Differences in histologic response (disappearance of DCIS) will be evaluated using Fisher's exact test. Correlation analysis and linear models will be used to evaluate associations among marker values at baseline and among changes in marker values and treatment. All statistical tests will be two-sided.
Time Frame	2-6 weeks from baseline to surgery, up to 6 weeks

Outcome Measure Data

Analysis Population Description

DCIS was present at the time of surgery in all patients.

Arm/Group Title	Arm I Lapatinib 1500 mg	Arm II Lapatinib 1000 mg	Arm III Lapatinib 750 mg	Arm IV Placebo
Arm/Group Description	Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.	Placebo orally once daily for 2-6 weeks until the time of surgery.
Measure Participants	2	10	0	10
Present	2 100%	10 100%	10 Infinity
Absent	0 0%	0 0%	0 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I Lapatinib 1500 mg, Arm II Lapatinib 1000 mg, Arm III Lapatinib 750 mg, Arm IV Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Biomarker Analysis of Proliferation Markers
Description	Correlation analysis and linear models will be used to evaluate associations among marker values at baseline and among changes in marker values and treatment. All statistical tests will be two-sided.
Time Frame	2-6 weeks from baseline to surgery, Up to 6 weeks

Outcome Measure Data

Analysis Population Description

No outcome data available due to laboratory issues affecting the analysis of biomarkers results.

Arm/Group Title	Arm I Lapatinib 1500 mg	Arm II Lapatinib 1000 mg	Arm III Lapatinib 750 mg	Arm IV Placebo
Arm/Group Description	Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.	Placebo orally once daily for 2-6 weeks until the time of surgery.
Measure Participants	0	0	0	0

4. Primary Outcome

Title	Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0
Description	Toxicity profile summarized reflects incidence by number of participants affected with adverse events by Maximum Grade 1 to 3, additional adverse event according to the NCI CTCAE version 3.0 reported in Adverse Event section results.
Time Frame	From baseline to 4-5 weeks after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I Lapatinib 1500 mg	Arm II Lapatinib 1000 mg	Arm III Lapatinib 750 mg	Arm IV Placebo
Arm/Group Description	Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.	Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.	Placebo orally once daily for 2-6 weeks until the time of surgery.
Measure Participants	2	10	0	10
Grade 3	0 0%	0 0%	1 Infinity
Grade 2	2 100%	6 60%	3 Infinity
Grade 1	0 0%	3 30%	4 Infinity

Adverse Events

Time Frame	Subjects followed up to 4-5 weeks after surgery to assess for adverse events with overall collection period approximately five years, first study period January 2008 to March 2010 and second September 2011 to August 2014.
Arm/Group Title	Arm I Lapatinib 1500 mg		Arm II Lapatinib 1000 mg		Arm III Lapatinib 750 mg		Arm IV Placebo
Arm/Group Description	Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.		Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.		Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.		Placebo orally once daily for 2-6 weeks until the time of surgery.
All Cause Mortality
	Arm I Lapatinib 1500 mg		Arm II Lapatinib 1000 mg		Arm III Lapatinib 750 mg		Arm IV Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I Lapatinib 1500 mg		Arm II Lapatinib 1000 mg		Arm III Lapatinib 750 mg		Arm IV Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/10 (0%)		0/0 (NaN)		1/10 (10%)
Infections and infestations
Infection	0/2 (0%)		0/10 (0%)		0/0 (NaN)		1/10 (10%)
Vascular disorders
Hematoma	0/2 (0%)		0/10 (0%)		0/0 (NaN)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	Arm I Lapatinib 1500 mg		Arm II Lapatinib 1000 mg		Arm III Lapatinib 750 mg		Arm IV Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		9/10 (90%)		0/0 (NaN)		8/10 (80%)
Blood and lymphatic system disorders
Lymphatics	0/2 (0%)		1/10 (10%)		0/0 (NaN)		1/10 (10%)
Endocrine disorders
Hot flashes/flushes	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Gastrointestinal disorders
Constipation	1/2 (50%)		1/10 (10%)		0/0 (NaN)		1/10 (10%)
Dehydration	0/2 (0%)		2/10 (20%)		0/0 (NaN)		0/10 (0%)
Diarrhea	2/2 (100%)		7/10 (70%)		0/0 (NaN)		2/10 (20%)
Dysphagia (difficulty swallowing)	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Heartburn/dyspepsia	1/2 (50%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Mucositis/stomatitis (clinical exam) Oral cavity	0/2 (0%)		1/10 (10%)		0/0 (NaN)		1/10 (10%)
Nausea	1/2 (50%)		4/10 (40%)		0/0 (NaN)		2/10 (20%)
Vomiting	1/2 (50%)		0/10 (0%)		0/0 (NaN)		1/10 (10%)
General disorders
Constitutional Symptoms	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Fatigue (asthenia, lethargy, malaise)	0/2 (0%)		2/10 (20%)		0/0 (NaN)		1/10 (10%)
Insomnia	1/2 (50%)		0/10 (0%)		0/0 (NaN)		0/10 (0%)
Pain	1/2 (50%)		3/10 (30%)		0/0 (NaN)		2/10 (20%)
Pain -Other	0/2 (0%)		2/10 (20%)		0/0 (NaN)		0/10 (0%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	0/2 (0%)		2/10 (20%)		0/0 (NaN)		0/10 (0%)
Infections and infestations
Infection	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Injury, poisoning and procedural complications
Cytokine release syndrome/acute infusion reaction	0/2 (0%)		0/10 (0%)		0/0 (NaN)		1/10 (10%)
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Magnesium, serum-low (hypomagnesemia)	0/2 (0%)		0/10 (0%)		0/0 (NaN)		1/10 (10%)
Nervous system disorders
Dizziness	0/2 (0%)		2/10 (20%)		0/0 (NaN)		1/10 (10%)
Neuropathy: sensory	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Renal and urinary disorders
Bladder spasms	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Renal/Genitourinary	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Urinary frequency/urgency	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/2 (50%)		0/10 (0%)		0/0 (NaN)		0/10 (0%)
Pulmonary/Upper Respiratory	0/2 (0%)		0/10 (0%)		0/0 (NaN)		2/10 (20%)
Skin and subcutaneous tissue disorders
Dermatology/Skin	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Dry skin	1/2 (50%)		3/10 (30%)		0/0 (NaN)		0/10 (0%)
Flushing	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Pruritus/itching	1/2 (50%)		1/10 (10%)		0/0 (NaN)		1/10 (10%)
Rash/desquamation	1/2 (50%)		3/10 (30%)		0/0 (NaN)		2/10 (20%)
Rash: acne/acneiform	1/2 (50%)		3/10 (30%)		0/0 (NaN)		2/10 (20%)
Vascular disorders
Hemorrhage, GI Rectum	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)
Hemorrhage, GU Vagina	1/2 (50%)		0/10 (0%)		0/0 (NaN)		0/10 (0%)
Hemorrhage, pulmonary/upper respiratory Nose	1/2 (50%)		0/10 (0%)		0/0 (NaN)		0/10 (0%)
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	0/2 (0%)		1/10 (10%)		0/0 (NaN)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.