AMG 706 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00574951
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 23
• Locations: 19
• Arm: 1
• Patients Per Site: 1.2

Study Details

Study Description

Brief Summary

RATIONALE: AMG 706 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well AMG 706 works in treating patients with persistent or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cavity Cancer	Drug: motesanib diphosphate	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To assess the activity of AMG 706, in terms of the frequency of patients with progression-free survival for at least 6 months after initiating therapy or with an objective tumor response, in patients with persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal carcinoma.

Secondary

• To determine the frequency and severity of adverse events as assessed by CTCAE v3.0.

• To characterize the distribution of the progression-free and overall survival of these patients.

OUTLINE: This is a multicenter study.

Patients receive oral AMG 706 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of AMG 706 (IND # 79,697) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMG 706 AMG 706 daily	Drug: motesanib diphosphate

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 [CT scan or MRI every other cycle for the first 6 months; then every 3 months thereafter; and at any other time if clinically indicated up to 5 years.]

   RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.

2. Progression-free Survival (PFS) at 6 Months [CT scan or MRI every other cycle for the first 6 months]

   Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. In this study, time of progression could not be validly collected due to the study being prematurely closed secondary to severe neurological adverse events seen in 4 patients,

Secondary Outcome Measures

1. Duration of Overall Survival (OS) [Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.]

   Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.

2. Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 [Assessed every cycle while on treatment, 30 days after the last cycle of treatment]

   Number of participants with a maximum grade of 3 or higher during the treatment period.

3. Duration of Progression-free Survival (PFS) [CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; then every 3 months thereafter; and at any other time if clinically indicated, up to 5 years]

   Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. In this study time of progression could not be validly collected due to the study being prematurely closed, secondary to severe neurological adverse events seen in 4 patients, and thus progression-free survival (PFS) cannot be presented. For safety reasons, most patients (16/22) were taken off study drug prior to progression (or AE),

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma

• Recurrent or persistent disease

• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan

• Must have at least one "target lesion" that can be used to assess response, as defined by RECIST criteria

• Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented OR a biopsy is obtained to confirm persistent disease ≥ 90 days following completion of radiotherapy

• Must have received one prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin, or another organoplatinum compound for management of primary disease

• Initial treatment may have included high-dose therapy, consolidation therapy, or extended therapy administered after surgical or non-surgical assessment

• One additional cytotoxic regimen for management of recurrent or persistent disease allowed

• Patients must have a platinum-free interval of < 12 months, have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy

• Ineligible for a higher priority GOG protocol

• No pleural effusion or ascites causing grade 2 or greater dyspnea

• No history of uncontrolled CNS metastases

• Patients with a history of CNS metastases must have their disease controlled by radiotherapy and/or surgery; have at least two imaging scans following treatment (that were no less than 30 days apart) showing no progression of any lesions and no new lesions; and be clinically stable off corticosteroids for ≥ 14 days prior to study randomization

PATIENT CHARACTERISTICS:

• GOG performance status (PS) 0-2* NOTE: *Patients who have received 2 prior regimen must have a GOG PS of 0-2 and patients who have received 2 prior regimens must have a GOG PS of 0-1

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Urine protein < 30 mg/dL by urinalyses or ≤ 1+ by urine dipstick (unless quantitative protein is < 500 mg by 24-hour urine collection)

• Bilirubin ≤ 1.5 times ULN (< 3 times ULN in patients with UGT1A1 promoter polymorphism [i.e., Gilbert syndrome] confirmed by genotyping or Invader® UGT1A1 Molecular Assay)

• AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)

• Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver or bone metastases are present)

• PTT normal

• INR ≤ 1.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Able to swallow oral medications

• Cardiac ejection fraction normal

• No sensory and motor neuropathy > grade 2

• No other invasive malignancies within the past 5 years, except nonmelanoma skin cancer or other specific malignancies

• No bleeding diathesis or hypercoagulopathy within the past 14 days

• No arterial or venous thrombosis within the past 12 months

• None of the following within the past 12 months:

• Myocardial infarction

• Cerebrovascular accident

• Transient ischemic attack

• Grade 2 or greater peripheral vascular disease

• Percutaneous transluminal coronary angioplasty/stent

• Congestive heart failure

• Ongoing arrhythmias requiring medication

• Unstable angina

• No average systolic blood pressure ≥ 150 mm Hg and average diastolic blood pressure ≥ 90 mm Hg

• Patients with hypertension that is stable on a current dose of anti-hypertensives are eligible

• No history of impaired cardiac status (e.g., severe heart disease, cardiomyopathy, or congestive heart failure)

• No psychiatric, addictive, or other kind of disorder that would compromise the ability of the patient to give written informed consent

• No open wounds, ulcers, or fractures

• No active infection requiring antibiotics (with the exception of uncomplicated UTI)

• No known HIV, hepatitis B, or hepatitis C positivity

• No known hypersensitivity to AMG 706

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered form prior surgery, radiotherapy, or chemotherapy

• At least 1 week since prior hormonal therapy for the malignant tumor

• Concurrent hormone replacement therapy allowed

• At least 3 weeks since other prior therapy directed at the malignant tumor, including biologic or immunologic agents (i.e., small molecules or murine monoclonal antibodies)

• At least 12 weeks since prior chimeric, human, or humanized monoclonal antibodies

• More than 30 days since prior investigational therapy

• More than 12 weeks since prior bevacizumab

• More than 30 days since prior VEGFR-targeted therapy, including, but not limited to, any of the following:

• SU5416

• SU6668

• Sunitinib malate

• Vandetanib

• Vatalanib

• AZD2171

• AEE 788

• Sorafenib

• More than 28 days since prior major surgery

• More than 14 days since prior minor surgery, including open breast biopsy

• More than 7 days since prior core needle biopsy or placement of a central venous access device (including portion, tunneled, or non-tunneled catheters)

• No prior cancer treatment that would contraindicate study therapy

• No prior therapy AMG 706

• No prior chemotherapy for any abdominal or pelvic tumor other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer

• Prior adjuvant chemotherapy for localized breast cancer allowed provided it was completed > 3 years ago, and the patient remains free of recurrent or metastatic disease

• No prior non-cytotoxic chemotherapy for management of recurrent or persistent disease

• No prior radiotherapy to any portion of the abdominal cavity or pelvis other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer

• Prior radiotherapy for localized cancer of the breast, head and neck, or skin allowed provided it was completed > 3 years ago, and the patient remains free of recurrent or metastatic disease

• No concurrent coumadin-type anticoagulants, including warfarin, at doses > 1 mg/day

• Concurrent low molecular weight heparin or low dose warfarin (i.e., ≤ 1 mg daily) for prophylaxis against central venous catheter thrombosis is allowed

• No other concurrent investigational or antineoplastic agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Saint Joseph Medical Center - Burbank	Burbank	California	United States	91505
2	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut	United States	06050
3	University of Illinois Cancer Center	Chicago	Illinois	United States	60612-7243
4	Rush University Medical Center	Chicago	Illinois	United States	60612
5	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois	United States	60521
6	St. Vincent Indianapolis Hospital	Indianapolis	Indiana	United States	46260
7	St. John's Regional Health Center	Springfield	Missouri	United States	65804
8	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
9	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
10	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
11	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
12	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
13	Lake/University Ireland Cancer Center	Mentor	Ohio	United States	44060
14	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
15	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
16	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
17	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
18	Harrington Cancer Center	Amarillo	Texas	United States	79106
19	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Russell J. Schilder, MD, Fox Chase Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT00574951
• Other Study ID Numbers: GOG-0170L; GOG-0170L; AMGEN-20060747
• First Posted: Dec 17, 2007
• Last Update Posted: Jan 11, 2018
• Last Verified: May 1, 2015

• Keywords provided by Gynecologic Oncology Group: fallopian tube cancer; recurrent ovarian epithelial cancer; primary peritoneal cavity cancer
• Additional relevant MeSH terms: Fallopian Tube Neoplasms; Motesanib diphosphate; Imetelstat

Study Results

Participant Flow

Recruitment Details	The study was activated on 12/10/2007 and closed to accrual on 4/22/2008.

Arm/Group Title	AMG 706
Arm/Group Description	AMG 706 125 mg PO daily continuously (one cycle is 28 days) until disease progression or adverse effects prohibit further therapy
Period Title: Overall Study
STARTED	23
COMPLETED	22
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	AMG 706
Arm/Group Description	AMG 706 125 mg PO daily continuously (one cycle is 28 days) until disease progression or adverse effects prohibit further therapy
Overall Participants	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.4 (9.6)
Age, Customized (Count of Participants)
50-59 years	7 31.8%
60-69 years	9 40.9%
70-79 years	5 22.7%
80-89 years	1 4.5%
Sex: Female, Male (Count of Participants)
Female	22 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0
Description	RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Time Frame	CT scan or MRI every other cycle for the first 6 months; then every 3 months thereafter; and at any other time if clinically indicated up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients.

Arm/Group Title	AMG 706
Arm/Group Description	AMG 706 125 mg PO daily continuously (one cycle is 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	22
Partial response	1 4.5%
Complete response	0 0%

2. Primary Outcome

Title	Progression-free Survival (PFS) at 6 Months
Description	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. In this study, time of progression could not be validly collected due to the study being prematurely closed secondary to severe neurological adverse events seen in 4 patients,
Time Frame	CT scan or MRI every other cycle for the first 6 months

Outcome Measure Data

Analysis Population Description

Time of progression could not be validly collected due to the study being prematurely closed due to severe neurological adverse events, thus 6-month PFS cannot be presented. For safety reasons, most patients (16/22) were taken off study drug prior to progression (or AE), and follow-up for progression after coming off study was not collected.

Arm/Group Title	AMG 706
Arm/Group Description	AMG 706 125 mg PO daily continuously (one cycle is 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	0

3. Secondary Outcome

Title	Duration of Overall Survival (OS)
Description	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Time Frame	Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients.

Arm/Group Title	AMG 706
Arm/Group Description	AMG 706 125 mg PO daily continuously (one cycle is 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	22
Median (95% Confidence Interval) [months]	13.1

4. Secondary Outcome

Title	Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Description	Number of participants with a maximum grade of 3 or higher during the treatment period.
Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	AMG 706
Arm/Group Description	AMG 706 125 mg PO daily continuously (one cycle is 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	22
Cardiac	2 9.1%
Gastrointestinal	5 22.7%
Hepatobiliary	1 4.5%
Metabolic	4 18.2%
Muskuloskeletal	1 4.5%
Other Neurological	4 18.2%
Pain	1 4.5%
Pulmonary	1 4.5%
Death, Not CTC coded	1 4.5%

5. Secondary Outcome

Title	Duration of Progression-free Survival (PFS)
Description	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. In this study time of progression could not be validly collected due to the study being prematurely closed, secondary to severe neurological adverse events seen in 4 patients, and thus progression-free survival (PFS) cannot be presented. For safety reasons, most patients (16/22) were taken off study drug prior to progression (or AE),
Time Frame	CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; then every 3 months thereafter; and at any other time if clinically indicated, up to 5 years

Outcome Measure Data

Analysis Population Description

Study Analysis aborted due to severe toxicities. Estimates not calculated. Follow up for progression after coming off study was not collected in a manner that yields time to time to progression data.

Arm/Group Title	AMG 706
Arm/Group Description	AMG 706 125 mg PO daily continuously (one cycle is 28 days) until disease progression or adverse effects prohibit further therapy
Measure Participants	0

Adverse Events

Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up
Arm/Group Title	AMG 706
Arm/Group Description	AMG 706 125 mg PO daily continuously (one cycle is 28 days) until disease progression or adverse effects prohibit further therapy
All Cause Mortality
	AMG 706
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	AMG 706
	Affected / at Risk (%)	# Events
Total	11/22 (50%)
Cardiac disorders
Hypertension	1/22 (4.5%)
Gastrointestinal disorders
Obstruction, Gi - Small Bowel Nos	2/22 (9.1%)
Vomiting	1/22 (4.5%)
General disorders
Death No Ctcae Term - Disease Progression Nos	1/22 (4.5%)
Hepatobiliary disorders
Cholecystitis	2/22 (9.1%)
Metabolism and nutrition disorders
Creatinine	1/22 (4.5%)
Musculoskeletal and connective tissue disorders
Fracture	1/22 (4.5%)
Nervous system disorders
Neurology - Other	1/22 (4.5%)
Seizure	1/22 (4.5%)
Confusion	1/22 (4.5%)
Other (Not Including Serious) Adverse Events
	AMG 706
	Affected / at Risk (%)	# Events
Total	21/22 (95.5%)
Blood and lymphatic system disorders
Neutrophils	2/22 (9.1%)
Platelets	2/22 (9.1%)
Leukocytes	7/22 (31.8%)
Hemoglobin	11/22 (50%)
Cardiac disorders
Palpitations	2/22 (9.1%)
Hypertension	9/22 (40.9%)
Ear and labyrinth disorders
Auditory/Ear - Other	1/22 (4.5%)
Tinnitus	1/22 (4.5%)
Endocrine disorders
Hot Flashes	2/22 (9.1%)
Hypothyroidism	3/22 (13.6%)
Eye disorders
Flashing Lights/Floaters	1/22 (4.5%)
Gastrointestinal disorders
Heartburn	2/22 (9.1%)
Mucositis (Functional/Sympt) - Oral Cavity	2/22 (9.1%)
Vomiting	4/22 (18.2%)
Anorexia	6/22 (27.3%)
Dehydration	1/22 (4.5%)
Constipation	3/22 (13.6%)
Nausea	11/22 (50%)
Diarrhea	9/22 (40.9%)
General disorders
Weight Loss	2/22 (9.1%)
Fatigue	15/22 (68.2%)
Pain: Chest /Thorax Nos	1/22 (4.5%)
Pain: Head/Headache	13/22 (59.1%)
Pain: Extremity-Limb	4/22 (18.2%)
Pain: Back	4/22 (18.2%)
Pain: Joint	2/22 (9.1%)
Pain: Bone	1/22 (4.5%)
Pain: Stomach	1/22 (4.5%)
Pain: Abdominal Pain Nos	4/22 (18.2%)
Pain: Skin	1/22 (4.5%)
Hepatobiliary disorders
Cholecystitis	1/22 (4.5%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	2/22 (9.1%)
Colitis, Infectious (Eg.C. Difficile)	1/22 (4.5%)
Inf W/Nml Or Gr 1 Or 2 Anc: Bladder	1/22 (4.5%)
Metabolism and nutrition disorders
Ast	7/22 (31.8%)
Creatinine	5/22 (22.7%)
Hypoalbuminemia	3/22 (13.6%)
Alt	5/22 (22.7%)
Alkaline Phosphatase	5/22 (22.7%)
Hypophosphatemia	2/22 (9.1%)
Hyponatremia	3/22 (13.6%)
Hypernatremia	1/22 (4.5%)
Hypocalcemia	5/22 (22.7%)
Hyperglycemia	6/22 (27.3%)
Hypokalemia	5/22 (22.7%)
Hypomagnesemia	2/22 (9.1%)
Musculoskeletal and connective tissue disorders
Muscle Weakness - Whole Body/Generalized	1/22 (4.5%)
Nervous system disorders
Neurology - Other	2/22 (9.1%)
Mood Alteration - Depression	1/22 (4.5%)
Seizure	2/22 (9.1%)
Cns Ischemia	1/22 (4.5%)
Confusion	1/22 (4.5%)
Dizziness	1/22 (4.5%)
Neuropathy-Sensory	6/22 (27.3%)
Neuropathy-Motor	1/22 (4.5%)
Respiratory, thoracic and mediastinal disorders
Cough	1/22 (4.5%)
Pleural Effusion	1/22 (4.5%)
Dyspnea	4/22 (18.2%)
Skin and subcutaneous tissue disorders
Rash	2/22 (9.1%)
Dry Skin	1/22 (4.5%)
Vascular disorders
Hemorrhage/Pulmonary - Nose	1/22 (4.5%)

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.