Trebananib in Treating Patients With Advanced Angiosarcoma That Cannot Be Removed by Surgery

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01623869
• Collaborator: (none)
• Enrollment: 16
• Locations: 70
• Arm: 1
• Duration (Months): 31
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well trebananib works in treating patients with advanced angiosarcoma that cannot be removed by surgery. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor.

Condition or Disease	Intervention/Treatment	Phase
Adult Angiosarcoma; Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma	Other: Laboratory Biomarker Analysis; Biological: Trebananib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the overall response rate (ORR), defined as complete response (CR) +partial response (PR), in patients with advanced, unresectable angiosarcoma treated with trebananib (AMG 386).

SECONDARY OBJECTIVES:

1. To evaluate the progression-free survival (PFS) and overall survival (OS) of patients with advanced, unresectable angiosarcoma treated with AMG 386.

TERTIARY OBJECTIVES:

1. To correlate ORR, PFS, and OS with: Baseline and post-treatment changes in expression of angiopoietin 2 (Ang2) and TEK tyrosine kinase, endothelial (Tie2) by immunohistochemistry (IHC); Serum levels of angiopoietin 1 (Ang1) and Ang2; Baseline and post-treatment changes in phospho-receptor tyrosine kinase status of TIE2, vascular endothelial growth factor receptor 2 (VEGFR-2), phosphatidylinositol 3 kinase (PI3K), mitogen-activated protein kinase Inhibitor (MEK) in tumor tissue; Mutational status of VEGFR-2 and amplification of v-myc myelocytomatosis viral oncogene homolog (avian) (MYC)/fms-related tyrosine kinase 4 (FLT4).

OUTLINE:

Patients receive trebananib intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then every 6 months for 18 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of the Angiopoietin-1 and -2 Peptibody AMG 386 for the Treatment of Angiosarcoma
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (trebananib) Patients receive 30 mg/kg trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Trebananib; Given IV; Other Names: AMG 386 Angiopoietin 1/2-Neutralizing Peptibody AMG 386

Outcome Measures

Primary Outcome Measures

1. Confirmed Response Rate (CR or PR) Using RECIST [Up to 18 months]

   Response and progression will be evaluated using the international RECIST guidelines (v1.1). Patients are evaluated every 8 weeks for disease status, with a subsequent 4 week assessment required to confirm a response. Complete Response (CR) - All of the following must be true: Disappearance of all target and non-target lesions, Each target lesion and non-target lymph node must have reduction in short axis to <1.0 cm. Partial Response (PR): At least a 30% decrease from the baseline measurements of the sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation. Persistence of one or more non-target lesions or non-target lymph nodes. The confirmed response rate is estimated as the number of patients having a CR or PR, divided by the number of eligible patients having at least one post-baseline assessment. The 95% confidence intervals provided using the method of Duffy and Santner.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [From the start of treatment to time of radiologic or clinical progression or death, whichever occurs first, assessed up to 18 months]

   Progression-free survival (PFS) is defined as the duration of time from the start of treatment to time of radiologic or clinical progression or death, whichever occurs first. PFS will be censored at most recent radiographic assessment date for patients remaining alive at the time of the statistical analysis. Kaplan-Meier methodology will be used to estimate the distribution of PFS.

2. OS [From the date of registration to the date of death or the date of last follow-up, assessed up to 18 months]

   Overall survival (OS) is the duration of time from the date of registration/randomization to the date of death or the date of last follow-up for patients who remain alive or who are lost to follow-up at the time of the analysis. Kaplan-Meier methodology will be used to estimate the distribution of OS.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically confirmed angiosarcoma that is unresectable

• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors(RECIST) 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam

• Patients must have had =< 4 prior systemic treatment regimens

• Eastern Cooperative Oncology Group (ECOG) 0-1 or Karnofsky >= 70%

• Life expectancy of greater than 3 months

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count >= 1,500/mcL

• Hemoglobin >= 8.5g/dL

• Platelet count >= 60,000/mcL

• Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 times institutional ULN

• Alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase[SGPT]) =< 2.5 times institutional ULN

• Partial thromboplastin time (PTT) or activated (a)PTT =< 1.5 times ULN per institutional laboratory range

• International normalized ratio(INR) =< 1.5 (unless on warfarin)

• Creatinine =< 1.5 times ULN OR creatinine clearance > 40 mL/min per 24-hour urine collection or calculated according to the Cockcroft-Gault formula

• Urinary protein =< 30 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1,000 mg in a 24-hour urine sample

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

• Breastfeeding must be discontinued if the mother is treated with AMG 386; these potential risks may also apply to other agents used in this study

• Female of childbearing potential is defined as the following: A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Generally well-controlled blood pressure with systolic blood pressure =< 150 mm Hg and diastolic blood pressure =< 90 mm Hg (Note: The use of anti-hypertensive medications to control hypertension is permitted)

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• No known history of brain metastases

• History of clinically significant bleeding within 6 months of enrollment/randomization

• No unresolved toxicities from prior systemic therapy that are Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 >= grade 2 in severity except alopecia

• Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor

• Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater (CTCAE version 4.0) peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent

• Major surgery within 28 days prior to enrollment or still recovering from prior surgery

• Treatment within 30 days prior to enrollment with strong immune modulators including, but not limited to, systemic cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide, lenalidomide, and targeted immune modulators such as abatacept (CTLA-4- -Ig),adalimumab, alefacept, anakinra, belatacept (LEA29Y), efalizumab, etanercept, infliximab, or rituximab

• Non-healing wound

• Subject not consenting to the use of highly effective contraceptive precautions (e.g., double barrier method [i.e., condom plus diaphragm]) during the course of the study and for 6 months after administration of the last study medication

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AMG 386

• History of allergic reactions to bacterially-produced proteins

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Patients who have not yet completed at least 21 days (30 days for prior monoclonal antibody therapy) since ending other investigational device or drug trials, or who are currently receiving other investigational treatments

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Non-pregnant, non-nursing; Note: Women of child bearing potential must have a pregnancy test, serum based within 7 days prior to registration; this is because AMG 386 is an inhibitor of angiogenesis with the potential for teratogenic or abortifacient effects

• Patients with a history of venous or arterial thromboembolism within 12 months prior to enrollment/randomization should be excluded

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beebe Medical Center	Lewes	Delaware	United States	19958
2	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
3	Washington Hospital Center	Washington	District of Columbia	United States	20010
4	Oncare Hawaii Inc-Pali Momi	Aiea	Hawaii	United States	96701
5	Pali Momi Medical Center	Aiea	Hawaii	United States	96701
6	Oncare Hawaii Inc-POB II	Honolulu	Hawaii	United States	96813
7	Queen's Medical Center	Honolulu	Hawaii	United States	96813
8	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
9	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
10	Oncare Hawaii Inc-Kuakini	Honolulu	Hawaii	United States	96817
11	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
12	Castle Medical Center	Kailua	Hawaii	United States	96734
13	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
14	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
15	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
16	Graham Hospital Association	Canton	Illinois	United States	61520
17	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
18	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
19	Memorial Hospital	Carthage	Illinois	United States	62321
20	Northwestern University	Chicago	Illinois	United States	60611
21	Eureka Hospital	Eureka	Illinois	United States	61530
22	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
23	Illinois CancerCare Galesburg	Galesburg	Illinois	United States	61401
24	Illinois CancerCare-Havana	Havana	Illinois	United States	62644
25	Mason District Hospital	Havana	Illinois	United States	62644
26	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
27	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
28	Mcdonough District Hospital	Macomb	Illinois	United States	61455
29	Holy Family Medical Center	Monmouth	Illinois	United States	61462
30	Illinois CancerCare-Monmouth	Monmouth	Illinois	United States	61462
31	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
32	Community Cancer Center Foundation	Normal	Illinois	United States	61761
33	Illinois CancerCare-Community Cancer Center	Normal	Illinois	United States	61761
34	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
35	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
36	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
37	Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
38	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
39	Proctor Hospital	Peoria	Illinois	United States	61614
40	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
41	Illinois Oncology Research Association CCOP	Peoria	Illinois	United States	61615
42	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
43	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
44	Illinois Valley Hospital	Peru	Illinois	United States	61354
45	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
46	Perry Memorial Hospital	Princeton	Illinois	United States	61356
47	Illinois CancerCare-Spring Valley	Spring Valley	Illinois	United States	61362
48	Carle Cancer Center	Urbana	Illinois	United States	61801
49	Franciscan Saint Francis Health-Indianapolis	Indianapolis	Indiana	United States	46237
50	Reid Hospital and Health Care Services	Richmond	Indiana	United States	47374
51	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
52	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
53	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51104
54	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
55	Union Hospital of Cecil County	Elkton MD	Maryland	United States	21921
56	Mayo Clinic	Rochester	Minnesota	United States	55905
57	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
58	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
59	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
60	Grandview Hospital	Dayton	Ohio	United States	45405
61	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
62	Miami Valley Hospital	Dayton	Ohio	United States	45409
63	Samaritan North Health Center	Dayton	Ohio	United States	45415
64	Dayton CCOP	Dayton	Ohio	United States	45420
65	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
66	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
67	Wayne Hospital	Greenville	Ohio	United States	45331
68	Kettering Medical Center	Kettering	Ohio	United States	45429
69	Upper Valley Medical Center	Troy	Ohio	United States	45373
70	Greene Memorial Hospital	Xenia	Ohio	United States	45385

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Sandra D'Angelo, Alliance for Clinical Trials in Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01623869
• Other Study ID Numbers: NCI-2012-01978; NCI-2012-01978; CDR0000735380; CALGB-A091103; A091103; A091103; U10CA180821; U10CA031946
• First Posted: Jun 20, 2012
• Last Update Posted: Oct 19, 2015
• Last Verified: Jun 1, 2015

• Additional relevant MeSH terms: Sarcoma; Hemangiosarcoma; Trebananib

Study Results

Participant Flow

Arm/Group Title	Treatment (Trebananib)
Arm/Group Description	Patients receive 30 mg/kg trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Trebananib)
Arm/Group Description	Patients receive 30 mg/kg trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Participants	16
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68.5
Sex: Female, Male (Count of Participants)
Female	10 62.5%
Male	6 37.5%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Confirmed Response Rate (CR or PR) Using RECIST
Description	Response and progression will be evaluated using the international RECIST guidelines (v1.1). Patients are evaluated every 8 weeks for disease status, with a subsequent 4 week assessment required to confirm a response. Complete Response (CR) - All of the following must be true: Disappearance of all target and non-target lesions, Each target lesion and non-target lymph node must have reduction in short axis to <1.0 cm. Partial Response (PR): At least a 30% decrease from the baseline measurements of the sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation. Persistence of one or more non-target lesions or non-target lymph nodes. The confirmed response rate is estimated as the number of patients having a CR or PR, divided by the number of eligible patients having at least one post-baseline assessment. The 95% confidence intervals provided using the method of Duffy and Santner.
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trebananib)
Arm/Group Description	Patients receive 30 mg/kg trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	16
Number (95% Confidence Interval) [percentage of participants]	0 0%

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression-free survival (PFS) is defined as the duration of time from the start of treatment to time of radiologic or clinical progression or death, whichever occurs first. PFS will be censored at most recent radiographic assessment date for patients remaining alive at the time of the statistical analysis. Kaplan-Meier methodology will be used to estimate the distribution of PFS.
Time Frame	From the start of treatment to time of radiologic or clinical progression or death, whichever occurs first, assessed up to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trebananib)
Arm/Group Description	Patients receive 30 mg/kg trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	16
Median (95% Confidence Interval) [months]	1.6

3. Secondary Outcome

Title	OS
Description	Overall survival (OS) is the duration of time from the date of registration/randomization to the date of death or the date of last follow-up for patients who remain alive or who are lost to follow-up at the time of the analysis. Kaplan-Meier methodology will be used to estimate the distribution of OS.
Time Frame	From the date of registration to the date of death or the date of last follow-up, assessed up to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Trebananib)
Arm/Group Description	Patients receive 30 mg/kg trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	16
Median (95% Confidence Interval) [months]	6.4

Adverse Events

Time Frame	Evaluated monthly from the date of randomization until 30 days following a patient's last dose.
Adverse Event Reporting Description	Maximum severity per AE classification is reported, per patient.
Arm/Group Title	Treatment (Trebananib)
Arm/Group Description	Patients receive 30 mg/kg trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Treatment (Trebananib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Trebananib)
	Affected / at Risk (%)	# Events
Total	6/16 (37.5%)
Cardiac disorders
Cardiac arrest	1/16 (6.3%)	1
Infections and infestations
Wound infection	1/16 (6.3%)	1
Investigations
Activated partial thromboplastin time prolonged	1/16 (6.3%)	1
Metabolism and nutrition disorders
Hypocalcemia	1/16 (6.3%)	1
Hyponatremia	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorders
Chest wall pain	1/16 (6.3%)	1
Nervous system disorders
Syncope	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)	1
Dyspnea	2/16 (12.5%)	2
Pleural effusion	1/16 (6.3%)	1
Respiratory failure	1/16 (6.3%)	1
Vascular disorders
Hematoma	1/16 (6.3%)	1
Thromboembolic event	2/16 (12.5%)	3
Other (Not Including Serious) Adverse Events
	Treatment (Trebananib)
	Affected / at Risk (%)	# Events
Total	12/16 (75%)
Blood and lymphatic system disorders
Anemia	3/16 (18.8%)	4
Gastrointestinal disorders
Mucositis oral	1/16 (6.3%)	1
Nausea	2/16 (12.5%)	2
General disorders
Edema face	2/16 (12.5%)	6
Edema limbs	7/16 (43.8%)	19
Fatigue	3/16 (18.8%)	3
Pain	1/16 (6.3%)	1
Immune system disorders
Allergic reaction	1/16 (6.3%)	1
Infections and infestations
Infections and infestations - Other, specify	1/16 (6.3%)	1
Urinary tract infection	1/16 (6.3%)	1
Investigations
Activated partial thromboplastin time prolonged	2/16 (12.5%)	6
Alanine aminotransferase increased	1/16 (6.3%)	1
Alkaline phosphatase increased	2/16 (12.5%)	3
Aspartate aminotransferase increased	3/16 (18.8%)	3
Blood bilirubin increased	1/16 (6.3%)	1
CD4 lymphocytes decreased	1/16 (6.3%)	3
Creatinine increased	1/16 (6.3%)	2
INR increased	2/16 (12.5%)	2
Lymphocyte count decreased	3/16 (18.8%)	5
Platelet count decreased	2/16 (12.5%)	4
Metabolism and nutrition disorders
Anorexia	1/16 (6.3%)	1
Hyperglycemia	2/16 (12.5%)	2
Hyperkalemia	1/16 (6.3%)	1
Hypoalbuminemia	3/16 (18.8%)	7
Hypocalcemia	2/16 (12.5%)	6
Hypokalemia	2/16 (12.5%)	3
Hyponatremia	4/16 (25%)	6
Metabolism and nutrition disorders - Other, specify	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/16 (6.3%)	1
Pain in extremity	1/16 (6.3%)	1
Nervous system disorders
Peripheral motor neuropathy	1/16 (6.3%)	2
Peripheral sensory neuropathy	1/16 (6.3%)	1
Renal and urinary disorders
Hematuria	1/16 (6.3%)	2
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)	1
Dyspnea	1/16 (6.3%)	1
Pleural effusion	1/16 (6.3%)	1
Pneumothorax	1/16 (6.3%)	1
Pulmonary edema	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Periorbital edema	2/16 (12.5%)	4
Rash acneiform	1/16 (6.3%)	1
Rash maculo-papular	2/16 (12.5%)	2
Vascular disorders
Hypertension	1/16 (6.3%)	1
Lymphedema	1/16 (6.3%)	1

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.