Bevacizumab With Abraxane in Patients With Recurrent Ovarian/ Peritoneal Cancer

• Sponsor: Accelerated Community Oncology Research Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT00407563
• Collaborator: Genentech, Inc. (Industry), Celgene Corporation (Industry)
• Enrollment: 48
• Locations: 11
• Duration (Months): 49
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness and tolerability of the combination of bevacizumab and Abraxane in the treatment of women with epithelial ovarian cancer or peritoneal cancer. The study will also evaluate how the patient's quality of life is during their treatment.

Condition or Disease	Intervention/Treatment	Phase
Epithelial Ovarian Cancer; Primary Peritoneal Carcinoma	Drug: Bevacizumab; Drug: Abraxane	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Bevacizumab With Abraxane in Patients With Recurrent, Platinum-Resistant Primary Epithelial Ovarian or Primary Peritoneal Carcinoma
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Feb 1, 2011

Outcome Measures

Primary Outcome Measures

1. 6-month Progression-Free Rate [6 months after initiation of study treatment]

   Progression-free rate is defined as the percentage of participants with no progression event at 6 months after starting study treatment. An event for this endpoint was defined as a progression-free survival event occurring earlier than six months, or discontinuation of treatment earlier than six months for any other reason. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.

Secondary Outcome Measures

1. Best Overall Response [Radiologic imaging was repeated after every 3 cycles (about every 12 weeks) during study treatment, up to 31 months.]

   Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR.

2. Overall Survival [Overall survival is defined as the time from treatment start until death from any cause, assessed up to 40 months.]

3. Progression-free Survival (PFS) [PFS was measured from day 1 of treatment until time of progression (assessed every 12 weeks) or death, whichever came first, assessed up to 30 months.]

   Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.

4. Best Overall Response at Six Months [Assessed over 6 months of study treatment]

   The outcome measure assessed the percentage of participants who had achieved either a Partial or Complete Response over 6 months of treatment. Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Measurable disease by CT or MRI.

• At least 1 "target lesion" to be used to assess response as defined by GOG RECIST criteria.

• ECOG performance status of 0 or 1.

• Patient provides voluntary written informed consent.

• At least 18 years of age.

• Negative serum pregnancy test.

• Recovered from any recent surgery for at least 30 days and is free of active infection.

• Received the following prior therapy at time of enrollment:

• Must have had 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin or organoplatinum. Initial therapy may have included high-dose therapy, consolidation, or extended therapy. Patient should be defined as recurrent or progression of disease within 6 months of last platinum chemotherapy.

• May have had 1 additional cytotoxic or non-cytotoxic chemotherapy regimen.

• Must have adequate hematologic and hepatic function.

Exclusion Criteria:

• Previously received bevacizumab.

• History of other invasive malignancy with the exception of nonmelanoma skin cancer.

• ECOG performance status of 2, 3, or 4.

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study. Patient must be bevacizumab naïve.

• Blood pressure of >150/100 mm Hg on antihypertensive medications.

• Prior history of hypertensive crisis or hypertensive encephalopathy.

• Diagnosed with unstable angina per NYHA or Grade 2 or greater congestive heart failure.

• History of myocardial infarction within 6 months of enrollment.

• History of stroke or transient ischemic attack within 6 months prior to study enrollment.

• Clinically significant vascular disease (e.g., aortic aneurysm, aortic dissection)or symptomatic peripheral vascular disease.

• Bleeding diathesis or coagulopathy.

• Presence of CNS or brain metastases.

• Pre-existing peripheral neuropathy of Grade ≥ 2.

• A major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study.

• A partial or complete small or large bowel obstruction demonstrated radiologically within 3 months prior to study enrollment.

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.

• Positive pregnancy test or is lactating.

• History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to study enrollment.

• Serious, non-healing wound, ulcer, or bone fracture.

• Serious intercurrent medical or psychiatric illness, including serious active infection.

• Inability to comply with study and/or follow-up procedures.

• Life expectancy of less than 12 weeks.

• Proteinuria at screening as demonstrated by either:

• Urine protein:creatinine (UPC) ratio ≥ 1.0 at screening OR

• Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).

• Known hypersensitivity to any component of bevacizumab.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Little Rock Hematology Oncology	Little Rock	Arkansas	United States	72205
2	Wilshire Oncology Medical Group, Inc.	La Verne	California	United States	91750
3	Northeast Georgia Cancer Care, LLC	Athens	Georgia	United States	30607
4	Southeastern Gynecologic Oncology, LLC	Atlanta	Georgia	United States	30342
5	North Idaho Cancer Center	Coeur d'Alene	Idaho	United States	38314
6	Hematology-Oncology Centers of the Northern Rockies	Billings	Montana	United States	59101
7	Mid-Ohio Oncology/Hematology	Columbus	Ohio	United States	43219
8	Pennsylvania Oncology Hematology Assoc.	Philadelphia	Pennsylvania	United States	19106
9	Chattanooga's Program in Women's Oncology	Chattanooga	Tennessee	United States	37403
10	The West Clinic	Memphis	Tennessee	United States	38120
11	Cancer Specialists of Tidewater, Ltd	Chesapeake	Virginia	United States	23320

Sponsors and Collaborators

• Accelerated Community Oncology Research Network
• Genentech, Inc.
• Celgene Corporation

Investigators

• Principal Investigator: Lee S. Schwartzberg, MD, FACP, The West Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Accelerated Community Oncology Research Network
• ClinicalTrials.gov Identifier: NCT00407563
• Other Study ID Numbers: ACORN ALSSOPR0501
• First Posted: Dec 5, 2006
• Last Update Posted: Apr 5, 2012
• Last Verified: Mar 1, 2012

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Ovarian Epithelial; Paclitaxel; Bevacizumab; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	9 community oncology research sites across the US within the ACORN network participated in this study. Enrollment started in January 2007 and was completed in December 2008.
Pre-assignment Detail	Informed consent was obtained from all subjects. All subjects underwent screening procedures to verify eligibility.

Arm/Group Title	Bevacizumab and Abraxane
Arm/Group Description	All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Period Title: Overall Study
STARTED	48
COMPLETED	47
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Bevacizumab and Abraxane
Arm/Group Description	All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Overall Participants	48
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	26 54.2%
>=65 years	22 45.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (10.22)
Sex: Female, Male (Count of Participants)
Female	48 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	48 100%

Outcome Measures

1. Primary Outcome

Title	6-month Progression-Free Rate
Description	Progression-free rate is defined as the percentage of participants with no progression event at 6 months after starting study treatment. An event for this endpoint was defined as a progression-free survival event occurring earlier than six months, or discontinuation of treatment earlier than six months for any other reason. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.
Time Frame	6 months after initiation of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab and Abraxane
Arm/Group Description	All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Measure Participants	48
Number (95% Confidence Interval) [percentage of patients]	62.5

2. Secondary Outcome

Title	Best Overall Response
Description	Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR.
Time Frame	Radiologic imaging was repeated after every 3 cycles (about every 12 weeks) during study treatment, up to 31 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab and Abraxane
Arm/Group Description	All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Measure Participants	48
Complete response	4 8.3%
Partial response	20 41.7%
Stable disease	14 29.2%
Progressive disease	8 16.7%
Not evaluable	2 4.2%

3. Secondary Outcome

Title	Overall Survival
Time Frame	Overall survival is defined as the time from treatment start until death from any cause, assessed up to 40 months.

Outcome Measure Data

Analysis Population Description

Participants who had not experienced death during or after stopping treatment were censored in the analysis.

Arm/Group Title	Bevacizumab and Abraxane
Arm/Group Description	All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Measure Participants	48
Median (95% Confidence Interval) [Months]	17.15

4. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.
Time Frame	PFS was measured from day 1 of treatment until time of progression (assessed every 12 weeks) or death, whichever came first, assessed up to 30 months.

Outcome Measure Data

Analysis Population Description

Participants who had not experienced either disease progression or death during or after stopping treatment were censored in the analysis.

Arm/Group Title	Bevacizumab and Abraxane
Arm/Group Description	All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Measure Participants	48
Median (95% Confidence Interval) [Months]	8.08

5. Secondary Outcome

Title	Best Overall Response at Six Months
Description	The outcome measure assessed the percentage of participants who had achieved either a Partial or Complete Response over 6 months of treatment. Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR.
Time Frame	Assessed over 6 months of study treatment

Outcome Measure Data

Analysis Population Description

The 2 tailed, 95% confidence interval of the estimated response rate was calculated using the normal approximation to the binomial distribution.

Arm/Group Title	Bevacizumab and Abraxane
Arm/Group Description	All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Measure Participants	48
Number (95% Confidence Interval) [percentage of patients]	50

Adverse Events

Time Frame	Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months.
Adverse Event Reporting Description	Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Arm/Group Title	Bevacizumab and Abraxane
Arm/Group Description	All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
All Cause Mortality
	Bevacizumab and Abraxane
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bevacizumab and Abraxane
	Affected / at Risk (%)	# Events
Total	13/48 (27.1%)
Blood and lymphatic system disorders
Neutropenia	1/48 (2.1%)
Pancytopenia	1/48 (2.1%)
Cardiac disorders
Cardio-respiratory arrest	1/48 (2.1%)
Gastrointestinal disorders
Abdominal distension	2/48 (4.2%)
Abdominal pain	2/48 (4.2%)
Colitis	1/48 (2.1%)
Constipation	1/48 (2.1%)
Intestinal perforation	1/48 (2.1%)
Nausea	1/48 (2.1%)
Small intestinal obstruction	5/48 (10.4%)
Vomiting	1/48 (2.1%)
General disorders
Hernia obstructive	1/48 (2.1%)
Pain	1/48 (2.1%)
Infections and infestations
Bronchitis	1/48 (2.1%)
Candidiasis	1/48 (2.1%)
Gastroenteritis	1/48 (2.1%)
Pneumonia	1/48 (2.1%)
Injury, poisoning and procedural complications
Overdoses	1/48 (2.1%)
Investigations
Body temperature increased	1/48 (2.1%)
Metabolism and nutrition disorders
Dehydration	1/48 (2.1%)
Renal and urinary disorders
Renal failure acute	1/48 (2.1%)
Vascular disorders
Deep vein thrombosis	2/48 (4.2%)
Hypotension	1/48 (2.1%)
Other (Not Including Serious) Adverse Events
	Bevacizumab and Abraxane
	Affected / at Risk (%)	# Events
Total	47/48 (97.9%)
Blood and lymphatic system disorders
Anemia	10/48 (20.8%)
Leukopenia	2/48 (4.2%)
Lymphadenopathy	1/48 (2.1%)
Lymphopenia	4/48 (8.3%)
Neutropenia	14/48 (29.2%)
Thrombocytopenia	1/48 (2.1%)
Cardiac disorders
Palpitations	1/48 (2.1%)
Ear and labyrinth disorders
External ear pain	1/48 (2.1%)
Tinnitus	1/48 (2.1%)
Eye disorders
Blepharitis	1/48 (2.1%)
Cataract	1/48 (2.1%)
Diplopia	1/48 (2.1%)
Dry eye	2/48 (4.2%)
Erythema of eyelid	2/48 (4.2%)
Eye hemorrhage	1/48 (2.1%)
Lacrimation increased	4/48 (8.3%)
Photopsia	2/48 (4.2%)
Vision blurred	1/48 (2.1%)
Gastrointestinal disorders
Abdominal distension	1/48 (2.1%)
Abdominal pain	11/48 (22.9%)
Abdominal pain lower	2/48 (4.2%)
Abdominal pain upper	3/48 (6.3%)
Ascites	1/48 (2.1%)
Colitis	1/48 (2.1%)
Constipation	16/48 (33.3%)
Diarrhea	16/48 (33.3%)
Dry mouth	3/48 (6.3%)
Dyspepsia	5/48 (10.4%)
Feces hard	1/48 (2.1%)
Gingival pain	1/48 (2.1%)
Glossodynia	3/48 (6.3%)
Hemorrhoids	2/48 (4.2%)
Nausea	18/48 (37.5%)
Oral pain	1/48 (2.1%)
Paresthesia oral	1/48 (2.1%)
Peritoneal and retroperitoneal disorders	1/48 (2.1%)
Proctalgia	2/48 (4.2%)
Rectal hemorrhage	1/48 (2.1%)
Reflux gastritis	1/48 (2.1%)
Small intestinal obstruction	1/48 (2.1%)
Sore mouth	1/48 (2.1%)
Stomatitis	11/48 (22.9%)
Toothache	1/48 (2.1%)
Vomiting	14/48 (29.2%)
General disorders
Asthenia	1/48 (2.1%)
Catheter site inflammation	1/48 (2.1%)
Chest pain	4/48 (8.3%)
Chills	4/48 (8.3%)
Fatigue	37/48 (77.1%)
Inflammation	1/48 (2.1%)
Influenza like illness	1/48 (2.1%)
Injection site reaction	1/48 (2.1%)
Local swelling	2/48 (4.2%)
Localized edema	2/48 (4.2%)
Malaise	1/48 (2.1%)
Nodule	1/48 (2.1%)
Edema peripheral	3/48 (6.3%)
Pain	5/48 (10.4%)
Pyrexia	1/48 (2.1%)
Hepatobiliary disorders
Hepatic pain	1/48 (2.1%)
Hepatomegaly	1/48 (2.1%)
Immune system disorders
Hypersensitivity	2/48 (4.2%)
Multiple allergies	2/48 (4.2%)
Infections and infestations
Bronchitis	1/48 (2.1%)
Candidiasis	1/48 (2.1%)
Catheter site infection	1/48 (2.1%)
Cellulitis	1/48 (2.1%)
Device related infection	1/48 (2.1%)
Fungal infection	1/48 (2.1%)
Gastroenteritis	1/48 (2.1%)
Hand-foot-and-mouth disease	1/48 (2.1%)
Infection	1/48 (2.1%)
Laryngitis	1/48 (2.1%)
Localized infection	2/48 (4.2%)
Nasopharyngitis	4/48 (8.3%)
Oral herpes	2/48 (4.2%)
Pharyngitis streptococcal	1/48 (2.1%)
Postpoperative wound infection	1/48 (2.1%)
Rhinitis	1/48 (2.1%)
Sepsis syndrome	1/48 (2.1%)
Sialoadenitis	1/48 (2.1%)
Sinusitis	7/48 (14.6%)
Streptococcal infection	1/48 (2.1%)
Tooth infection	1/48 (2.1%)
Upper respiratory tract infection	8/48 (16.7%)
Urinary tract infection	11/48 (22.9%)
Vaginal infection	2/48 (4.2%)
Vaginitis bacterial	1/48 (2.1%)
Wound infection	1/48 (2.1%)
Injury, poisoning and procedural complications
Chest injury	1/48 (2.1%)
Contusion	1/48 (2.1%)
Joint sprain	2/48 (4.2%)
Post procedural hemorrhage	1/48 (2.1%)
Postoperative ileus	1/48 (2.1%)
Procedural pain	1/48 (2.1%)
Procedural site reaction	3/48 (6.3%)
Skin laceration	1/48 (2.1%)
Investigations
Aspartate aminotransferase increased	2/48 (4.2%)
Blood creatinine increased	1/48 (2.1%)
Blood lactate dehydrogenase increased	2/48 (4.2%)
Blood pressure increased	2/48 (4.2%)
Blood thyroid stimulating hormone increased	1/48 (2.1%)
Body temperature increased	4/48 (8.3%)
C-reactive protein increased	1/48 (2.1%)
CD4 lymphocytes increased	1/48 (2.1%)
Forced expiratory volume	1/48 (2.1%)
Hematocrit decreased	1/48 (2.1%)
Hemoglobin decreased	2/48 (4.2%)
Monoctye count increased	1/48 (2.1%)
Neutrophil count decreased	4/48 (8.3%)
Parasite stool test positive	1/48 (2.1%)
Platelet count decreased	1/48 (2.1%)
Red blood cell count decreased	1/48 (2.1%)
White blood cell count decreased	4/48 (8.3%)
Metabolism and nutrition disorders
Decreased appetite	8/48 (16.7%)
Dehydration	1/48 (2.1%)
Fluid retention	1/48 (2.1%)
Hypercalcemia	1/48 (2.1%)
Hyperglycemia	4/48 (8.3%)
Hyperkalemia	4/48 (8.3%)
Hypermagnesemia	1/48 (2.1%)
Hypernatremia	1/48 (2.1%)
Hyperphosphatemia	1/48 (2.1%)
Hypoglycemia	1/48 (2.1%)
Hypokalemia	2/48 (4.2%)
Hypomagnesemia	6/48 (12.5%)
Hypophosphatemia	1/48 (2.1%)
Weight loss poor	3/48 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	14/48 (29.2%)
Arthritis	1/48 (2.1%)
Back pain	5/48 (10.4%)
Flank pain	1/48 (2.1%)
Foot fracture	1/48 (2.1%)
Groin pain	2/48 (4.2%)
Joint stiffness	2/48 (4.2%)
Joint swelling	2/48 (4.2%)
Muscle spasms	3/48 (6.3%)
Muscular weakness	2/48 (4.2%)
Musculoskeletal discomfort	1/48 (2.1%)
Musculoskeletal pain	3/48 (6.3%)
Myalgia	6/48 (12.5%)
Osteoporosis	1/48 (2.1%)
Pain in extremity	9/48 (18.8%)
Plantar fasciitis	1/48 (2.1%)
Temporomandibular joint syndrome	1/48 (2.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumor benign	1/48 (2.1%)
Nervous system disorders
Dizziness	5/48 (10.4%)
Dysgeusia	7/48 (14.6%)
Encephalopathy	1/48 (2.1%)
Headache	12/48 (25%)
Hypoesthesia	4/48 (8.3%)
Memory impairment	3/48 (6.3%)
Nerve compression	1/48 (2.1%)
Neuralgia	1/48 (2.1%)
Neuropathy peripheral	15/48 (31.3%)
Paresthesia	1/48 (2.1%)
Sciatica	1/48 (2.1%)
Sinus headache	2/48 (4.2%)
Psychiatric disorders
Anxiety	3/48 (6.3%)
Depression	2/48 (4.2%)
Disturbance in attention	1/48 (2.1%)
Insomnia	9/48 (18.8%)
Mood altered	1/48 (2.1%)
Nightmare	1/48 (2.1%)
Renal and urinary disorders
Dysuria	6/48 (12.5%)
Hematuria	1/48 (2.1%)
Micturition urgency	1/48 (2.1%)
Proteinuria	6/48 (12.5%)
Urethral pain	1/48 (2.1%)
Reproductive system and breast disorders
Breast pain	1/48 (2.1%)
Edema genital	1/48 (2.1%)
Pelvic pain	1/48 (2.1%)
Sexual dysfunction	1/48 (2.1%)
Vaginal discharge	1/48 (2.1%)
Vaginal hemorrhage	2/48 (4.2%)
Vulvovaginal dryness	3/48 (6.3%)
Vulvovaginal pruritis	1/48 (2.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/48 (2.1%)
Cough	11/48 (22.9%)
Dysphonia	9/48 (18.8%)
Dyspnea	10/48 (20.8%)
Dyspnea exertional	3/48 (6.3%)
Epistaxis	23/48 (47.9%)
Hemoptysis	1/48 (2.1%)
Nasal congestion	3/48 (6.3%)
Oropharyngeal pain	5/48 (10.4%)
Paranasal sinus discomfort	2/48 (4.2%)
Pneumothorax	1/48 (2.1%)
Postnasal drip	1/48 (2.1%)
Respiratory tract congestion	1/48 (2.1%)
Rhinitis allergic	2/48 (4.2%)
Rhinorrhea	6/48 (12.5%)
Sinus congestion	2/48 (4.2%)
Sinus disorder	1/48 (2.1%)
Sinus disorder, NOS	2/48 (4.2%)
Skin and subcutaneous tissue disorders
Acne	1/48 (2.1%)
Alopecia	15/48 (31.3%)
Blister	1/48 (2.1%)
Dermatitis acneiform	1/48 (2.1%)
Dry skin	1/48 (2.1%)
Nail discoloration	1/48 (2.1%)
Nail disorder	4/48 (8.3%)
Onychomadesis	1/48 (2.1%)
Pruritus	4/48 (8.3%)
Rash	4/48 (8.3%)
Skin discoloration	1/48 (2.1%)
Skin disorder	1/48 (2.1%)
Skin hyperpigmentation	1/48 (2.1%)
Umbilical hemorrhage	1/48 (2.1%)
Surgical and medical procedures
Ileostomy	1/48 (2.1%)
Tooth extraction	1/48 (2.1%)
Vascular disorders
Flushing	1/48 (2.1%)
Hot flush	1/48 (2.1%)
Hypertension	10/48 (20.8%)
Hypotension	3/48 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Proposed publication must be submitted to Funder at least 60 days prior to the submission for publication. If Funder requests in writing, the proposed publication may be held for an additional 90 days.