Bevacizumab in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer or Primary Peritoneal Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00022659
• Collaborator: Gynecologic Oncology Group (Other)
• Enrollment: 64
• Location: 1
• Arm: 1
• Duration (Months): 95
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This phase II trial is to see if bevacizumab works in treating patients who have persistent or recurrent ovarian epithelial cancer or primary peritoneal cancer. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them.

Condition or Disease	Intervention/Treatment	Phase
Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer	Biological: bevacizumab; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the 6-month progression-free survival of patients with persistent or recurrent ovarian epithelial or primary peritoneal cancer treated with bevacizumab.

2. Determine the nature and degree of toxicity of this drug in these patients. III. Determine the progression-free and overall survival of patients treated with this drug.

3. Determine the frequency of clinical response in patients treated with this drug.

4. Determine the effect of this drug on initial performance status, age, and mucinous or clear cell histology in these patients.

5. Correlate biological and imaging markers with 6-month progression-free survival of patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Bevacizumab (Anti-VEGF Humanized Monoclonal Antibody) (NSC #704865) in the Treatment of Persistent or Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma
• Study Start Date: Apr 1, 2002
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (bevacizumab) Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Biological: bevacizumab; Given IV; Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival at 6 Months [Every other cycle for 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.

2. Tumor Response [Every other cycle for the first 6 months; then every 3 months x 2 ; then every 6 months thereafter for 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.

3. Number of Participants and Degree of Toxicity of Bevacizumab in This Cohort of Patients as Assessed by CTC. [Assessed every cycle while on treatment, 30 days after the last cycle of treatment, up to 5 years.]

Secondary Outcome Measures

1. Overall Survival [From study entry to death or last contact, up to 5 years.]

   The observed length of life from entry into the study to death or the date of last contact.

2. Duration of Progression-free Survival [Every other cycle for the first 6 months; then every 3 months x 2 ; then every 6 months therafter for up to 5 years.]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed ovarian epithelial or primary peritoneal carcinoma

• Recurrent or persistent after initial standard surgery or chemotherapy

• Incurable with standard surgery, chemotherapy, or radiotherapy

• At least 1 unidimensionally measurable target lesion

• At least 20 mm by conventional techniques

• At least 10 mm by spiral CT scan

• Outside the area of prior radiotherapy

• Accessible to guided core needle biopsy

• Received 1 prior platinum-based chemotherapy regimen (e.g., carboplatin, cisplatin, or another organoplatinum compound) for primary disease

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

• Patients with only 1 prior platinum-based chemotherapy regimen must have an initial treatment-free interval of less than 12 months

• Patients with an initial treatment-free interval of more than 12 months must have progressive disease after prior platinum-based chemotherapy regimen as second-line therapy

• No tumors involving major blood vessels

• No evidence of CNS disease (primary brain tumor or brain metastases) within the past 5 years

• Ineligible for higher priority Gynecologic Oncology Group (GOG) protocols (i.e., active phase III GOG protocols for the same patient population)

• Performance status - GOG 0-2 (patients who have received 1 prior regimen)

• Performance status - GOG 0-1 (patients who have received 2 prior regimens)

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• No known bleeding disorder or coagulopathy

• No active bleeding

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

• serum glutamate oxaloacetate transaminase (SGOT) ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• PT (INR) ≤ 1.5 (INR 2-3 if on stable dose of therapeutic warfarin or low molecular weight heparin)

• Partial thromboplastin time (PTT) < 1.2 times control

• Creatinine ≤ 1.5 times ULN

• Creatinine clearance > 60 mL/min

• No proteinuria, as indicated by 1 of the following:

• Negative urine dipstick

• Urine protein < 30 mg/dL

• Urine protein < 1,000 mg on 24-hour urine collection

• No clinically significant cardiovascular disease, including any of the following:

• Uncontrolled hypertension

• Myocardial infarction within the past 6 months

• Unstable angina within the past 6 months

• New York Heart Association class II-IV congestive heart failure

• Serious cardiac arrhythmia requiring medication

• Peripheral vascular disease ≥ grade 2

• No stroke within the past 5 years

• No pathologic condition that carries a high risk of bleeding

• No significant traumatic injury within the past 28 days

• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

• No uncontrolled seizures within the past 5 years

• No neuropathy (motor and sensory) ≥ grade 2

• No serious non-healing wound, ulcer, or bone fracture

• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• No active infection requiring parenteral antibiotics

• No known claustrophobia that would preclude MRI tolerance

• No ferromagnetic implants or pacers

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for at least 3 months after study treatment

• At least 3 weeks since prior immunologic therapy directed at malignancy

• No prior bevacizumab

• No other concurrent immunotherapy directed at malignancy

• One additional prior cytotoxic regimen for recurrent or persistent disease allowed

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

• No concurrent chemotherapy directed at malignancy

• At least 1 week since prior hormonal therapy directed at malignancy

• No concurrent hormonal therapy directed at malignancy

• Concurrent hormone replacement therapy allowed

• Recovered from prior radiotherapy

• No concurrent radiotherapy directed at malignancy

• At least 28 days since prior major surgery or open biopsy and recovered

• At least 7 days since prior core biopsy or placement of vascular access device

• No anticipated need for major surgical procedure during study participation

• At least 3 weeks since other prior therapy directed at malignancy

• No prior anticancer therapy that would preclude study entry

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gynecologic Oncology Group	Philadelphia	Pennsylvania	United States	19103

Sponsors and Collaborators

• National Cancer Institute (NCI)
• Gynecologic Oncology Group

Investigators

• Principal Investigator: Robert Burger, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00022659
• Other Study ID Numbers: NCI-2012-02400; NCI-2012-02400; CDR0000068839; GOG-0170D; GOG-0170D; U10CA027469
• First Posted: Jan 27, 2003
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Carcinoma, Ovarian Epithelial; Recurrence; Bevacizumab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	The study was activated on 4/29/2002 and closed to accrual on 8/25/2004 (suspended from 10/6/2003 to 12/1/2003).

Arm/Group Title	Bevacizumab
Arm/Group Description	Bevacizumab 15 mg/kg IV, every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
Period Title: Overall Study
STARTED	64
COMPLETED	62
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Bevacizumab
Arm/Group Description	Bevacizumab 15 mg/kg IV, every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
Overall Participants	62
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.6 (12.5)
Age, Customized (participants) [Number]
10-19 years	1 1.6%
20-29 years	1 1.6%
30-39 years	3 4.8%
40-49 years	13 21%
50-59 years	21 33.9%
60-69 years	13 21%
70-79 years	10 16.1%
Sex: Female, Male (Count of Participants)
Female	62 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	62 100%
Histologic Type (participants) [Number]
Adenocarcinoma, Unspecified	1 1.6%
Clear Cell Carcinoma	2 3.2%
Endometrioid Adenocarcinoma	2 3.2%
Mixed Epithelial Carcinoma	6 9.7%
Serous Adenocarcinoma	51 82.3%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival 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.
Time Frame	Every other cycle for 6 months.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients.

Arm/Group Title	Bevacizumab
Arm/Group Description	Bevacizumab 15 mg/kg IV, every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
Measure Participants	62
Number (90% Confidence Interval) [percentage of participants]	40.3 65%

2. Primary Outcome

Title	Tumor Response
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	Every other cycle for the first 6 months; then every 3 months x 2 ; then every 6 months thereafter for up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients.

Arm/Group Title	Bevacizumab
Arm/Group Description	Bevacizumab 15 mg/kg IV, every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
Measure Participants	62
Number (90% Confidence Interval) [percentage of participants]	21 33.9%

3. Primary Outcome

Title	Number of Participants and Degree of Toxicity of Bevacizumab in This Cohort of Patients as Assessed by CTC.
Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment, up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Grade 1 (CTCAE v 2.0)	Grade 2 (CTCAE v 2.0)	Grade 3 (CTCAE v 2.0)	Grade 4 (CTCAE v 2.0)
Arm/Group Description	Number of patients who experienced a grade 1 event using Common Toxicity Criteria version 2.0	Number of patients who experienced a grade 2 event using Common Toxicity Criteria version 2.0	Number of patients who experienced a grade 3 event using Common Toxicity Criteria version 2.0	Number of patients who experienced a grade 4 event using Common Toxicity Criteria version 2.0
Measure Participants	62	62	62	62
Leukopenia	18 29%	0 NaN	0 NaN	0 NaN
Thrombocytopenia	6 9.7%	0 NaN	0 NaN	0 NaN
Neutropenia	6 9.7%	3 NaN	0 NaN	0 NaN
Anemia	18 29%	1 NaN	0 NaN	0 NaN
Hematologic	2 3.2%	1 NaN	1 NaN	0 NaN
Allergy	3 4.8%	0 NaN	2 NaN	0 NaN
Hearing	2 3.2%	0 NaN	0 NaN	0 NaN
Cardiovascular	12 19.4%	1 NaN	7 NaN	1 NaN
Coagulation	9 14.5%	2 NaN	1 NaN	0 NaN
Constitutional	22 35.5%	6 NaN	1 NaN	0 NaN
Dermatologic	10 16.1%	2 NaN	0 NaN	0 NaN
Endocrine	3 4.8%	0 NaN	0 NaN	0 NaN
Gastrointestinal	26 41.9%	6 NaN	3 NaN	1 NaN
Genitourinary/Renal	5 8.1%	14 NaN	0 NaN	1 NaN
Hemorrhage	14 22.6%	0 NaN	0 NaN	0 NaN
Hepatic	19 30.6%	2 NaN	1 NaN	0 NaN
Infection	3 4.8%	6 NaN	0 NaN	0 NaN
Lymphatics	2 3.2%	0 NaN	0 NaN	0 NaN
Musculoskeletal	4 6.5%	1 NaN	0 NaN	0 NaN
Metabolic	17 27.4%	0 NaN	0 NaN	0 NaN
Neurologic	16 25.8%	1 NaN	0 NaN	0 NaN
Ocular	2 3.2%	1 NaN	0 NaN	0 NaN
Pain	26 41.9%	6 NaN	3 NaN	0 NaN
Pulmonary	6 9.7%	6 NaN	1 NaN	0 NaN
Sexual/Reproductive	2 3.2%	0 NaN	0 NaN	0 NaN

4. Secondary Outcome

Title	Overall Survival
Description	The observed length of life from entry into the study to death or the date of last contact.
Time Frame	From study entry to death or last contact, up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients.

Arm/Group Title	Bevacizumab
Arm/Group Description	Bevacizumab 15 mg/kg IV, every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
Measure Participants	62
Median (95% Confidence Interval) [months]	16.9

5. Secondary Outcome

Title	Duration of Progression-free Survival
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.
Time Frame	Every other cycle for the first 6 months; then every 3 months x 2 ; then every 6 months therafter for up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Bevacizumab
Arm/Group Description	Bevacizumab 15 mg/kg IV, every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
Measure Participants	62
Median (Inter-Quartile Range) [months]	4.7

Adverse Events

Time Frame	All Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adverse Events (SAEs) up to 5 years after stopping study treatment
Arm/Group Title	Bevacizumab
Arm/Group Description	Bevacizumab 15 mg/kg IV, every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
All Cause Mortality
	Bevacizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bevacizumab
	Affected / at Risk (%)	# Events
Total	26/62 (41.9%)
Blood and lymphatic system disorders
Neutropenia	2/62 (3.2%)
Leukopenia	1/62 (1.6%)
Anemia	1/62 (1.6%)
Hematologic Other	1/62 (1.6%)
Cardiac disorders
Edema	1/62 (1.6%)
Thrombosis Embolism	2/62 (3.2%)
Ischemia/Cardiac Infarction	1/62 (1.6%)
Gastrointestinal disorders
Ileus	1/62 (1.6%)
Constipation	2/62 (3.2%)
Vomitting	1/62 (1.6%)
Nausea	2/62 (3.2%)
Gi Other	2/62 (3.2%)
General disorders
Weight Gain(No Vod)	1/62 (1.6%)
Abdominal Pain	1/62 (1.6%)
Pain Tumor	1/62 (1.6%)
Immune system disorders
Allergic Reaction	1/62 (1.6%)
Renal and urinary disorders
Proteinuria	1/62 (1.6%)
Respiratory, thoracic and mediastinal disorders
Voice Changes/Stridor/Larynx	1/62 (1.6%)
Dyspnea	2/62 (3.2%)
Skin and subcutaneous tissue disorders
Flushing	1/62 (1.6%)
Vascular disorders
Partial Thromboplastin Time	1/62 (1.6%)
Melena/Gi Bleeding	1/62 (1.6%)
Other (Not Including Serious) Adverse Events
	Bevacizumab
	Affected / at Risk (%)	# Events
Total	62/62 (100%)
Blood and lymphatic system disorders
Neutropenia	13/62 (21%)
Thrombocytopenia	8/62 (12.9%)
Lymphopenia	4/62 (6.5%)
Leukopenia	22/62 (35.5%)
Transfusion Prbc's	2/62 (3.2%)
Anemia	30/62 (48.4%)
Hematologic Other	1/62 (1.6%)
Lymphatics Other	1/62 (1.6%)
Lymphatics	2/62 (3.2%)
Cardiac disorders
Conduction Abnorm Atrioventricular Block	1/62 (1.6%)
Hypotension	3/62 (4.8%)
Sinus Tachycardia	4/62 (6.5%)
Arrhythmia Super Ventricular	1/62 (1.6%)
Phlebitis Superficial	1/62 (1.6%)
Sinus Bradycardia	1/62 (1.6%)
Edema	10/62 (16.1%)
Thrombosis Embolism	3/62 (4.8%)
Hypertension	18/62 (29%)
Palpitations	1/62 (1.6%)
Ischemia/Cardiac Infarction	1/62 (1.6%)
Ear and labyrinth disorders
Inner Ear/Hearing	4/62 (6.5%)
Middle Ear/Hearing	1/62 (1.6%)
Endocrine disorders
Hypothyroidism	2/62 (3.2%)
Hot Flashes/Flushes	8/62 (12.9%)
Eye disorders
Glaucoma	1/62 (1.6%)
Ocular Other	2/62 (3.2%)
Tearing	1/62 (1.6%)
Dry Eye	2/62 (3.2%)
Cataract	3/62 (4.8%)
Vision Blurres	2/62 (3.2%)
Gastrointestinal disorders
Anorexia	12/62 (19.4%)
Flatulence	4/62 (6.5%)
Diarrhea With Colostomy	1/62 (1.6%)
Mouth Dryness	2/62 (3.2%)
Ileus	3/62 (4.8%)
Gastritis	3/62 (4.8%)
Ascites Non-Malignant	1/62 (1.6%)
Proctitis	1/62 (1.6%)
Dyspepsia/Heartburn	10/62 (16.1%)
Taste Disturbance	1/62 (1.6%)
Dysphagia Esophagitis Odynophagia	4/62 (6.5%)
Diarrhea Without Colostomy	18/62 (29%)
Constipation	24/62 (38.7%)
Stomatitis/Pharyngitis	11/62 (17.7%)
Dehydration	3/62 (4.8%)
Vomitting	21/62 (33.9%)
Nausea	27/62 (43.5%)
Gi Other	13/62 (21%)
General disorders
Fever(No Neutropenia)	5/62 (8.1%)
Weight Loss	8/62 (12.9%)
Rigors Chills	3/62 (4.8%)
Weight Gain(No Vod)	2/62 (3.2%)
Sweating	3/62 (4.8%)
Fatigue	40/62 (64.5%)
Abdominal Pain	29/62 (46.8%)
Pain Other	14/62 (22.6%)
Pain Tumor	5/62 (8.1%)
Pleuritic Pain	2/62 (3.2%)
Neuropathic Pain	1/62 (1.6%)
Earache	1/62 (1.6%)
Dyspareunia	2/62 (3.2%)
Headache	19/62 (30.6%)
Pelvic Pain	7/62 (11.3%)
Chest Pain	6/62 (9.7%)
Bone Pain	3/62 (4.8%)
Arthralgia	14/62 (22.6%)
Myalgia	17/62 (27.4%)
Pain Rectal/Perirectal	1/62 (1.6%)
Hepatobiliary disorders
Ggt(Gamma-Glutamyltranspeptidase)	1/62 (1.6%)
Hepatic Other	2/62 (3.2%)
Hypoalbuminemia	12/62 (19.4%)
Sgot(Alt)	11/62 (17.7%)
Sgot(Ast)	19/62 (30.6%)
Alkaline Phosphatase	17/62 (27.4%)
Bilirubin	4/62 (6.5%)
Immune system disorders
Allergic Rhinitis	8/62 (12.9%)
Allergic Reaction	3/62 (4.8%)
Infections and infestations
Infection Without Neutropenia	26/62 (41.9%)
Metabolism and nutrition disorders
Alkalosis	1/62 (1.6%)
Hypercholesterolemia	4/62 (6.5%)
Hypophosphatemia	8/62 (12.9%)
Metabolic Other	14/62 (22.6%)
Hyponatremia	11/62 (17.7%)
Hyperuricemia	1/62 (1.6%)
Hypertyiglyceridemia	3/62 (4.8%)
Bicarbonate	1/62 (1.6%)
Hypernatremia	2/62 (3.2%)
Hypocalcemia	8/62 (12.9%)
Hypermagnesemia	3/62 (4.8%)
Hyperkalemia	6/62 (9.7%)
Hyperglycemia	16/62 (25.8%)
Hypoglycemia	5/62 (8.1%)
Hypokalemia	3/62 (4.8%)
Hypercalcemia	3/62 (4.8%)
Hypomagnesmia	12/62 (19.4%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Other	3/62 (4.8%)
Arthritis	7/62 (11.3%)
Muscle Weakness	4/62 (6.5%)
Nervous system disorders
Extrapyramidal	1/62 (1.6%)
Depressed Level Of Consciousness	1/62 (1.6%)
Vertigo	1/62 (1.6%)
Mood Alteration Anxeity/Agitation	16/62 (25.8%)
Memory Loss	2/62 (3.2%)
Insomnia	6/62 (9.7%)
Dizziness	9/62 (14.5%)
Mood Alteration Depression	9/62 (14.5%)
Neuropathy Sensor	15/62 (24.2%)
Pyramidal Tract Dysfunction	1/62 (1.6%)
Renal and urinary disorders
Urinary Frequency/Urgency	5/62 (8.1%)
Dysuria	5/62 (8.1%)
Creatinine	4/62 (6.5%)
Renal/Gu Other	3/62 (4.8%)
Vaginitis No Infection	4/62 (6.5%)
Ureteral Obstruction	1/62 (1.6%)
Incontinence	1/62 (1.6%)
Hemoglobinuria	1/62 (1.6%)
Bladder Spasms	1/62 (1.6%)
Proteinuria	22/62 (35.5%)
Reproductive system and breast disorders
Vaginal Dryness	3/62 (4.8%)
Libido	1/62 (1.6%)
Respiratory, thoracic and mediastinal disorders
Voice Changes/Stridor/Larynx	7/62 (11.3%)
Pulmonary Other	1/62 (1.6%)
Cough	8/62 (12.9%)
Apnea	1/62 (1.6%)
Ards	1/62 (1.6%)
Pneumonitis/Pulmonary Infiltrates	1/62 (1.6%)
Pleural Effusion	1/62 (1.6%)
Dyspnea	16/62 (25.8%)
Skin and subcutaneous tissue disorders
Pruritis	4/62 (6.5%)
Alopecia	6/62 (9.7%)
Rash Desquamation	7/62 (11.3%)
Skin Other	1/62 (1.6%)
Nail Changes	3/62 (4.8%)
Pigmentation Changes	1/62 (1.6%)
Photosensitivity	1/62 (1.6%)
Hand-Foot Skin Reaction	1/62 (1.6%)
Bruising	3/62 (4.8%)
Dry Skin	3/62 (4.8%)
Vascular disorders
Prothrombin Time	1/62 (1.6%)
Coagulation Other	8/62 (12.9%)
Partial Thromboplastin Time	10/62 (16.1%)
Hemorrhage Other	4/62 (6.5%)
Rectal Bleeding/Hematochezia	4/62 (6.5%)
Epistaxis	6/62 (9.7%)
Melena/Gi Bleeding	1/62 (1.6%)
Hemorrhage Without Grade 3/4 Thrombocytopenia	2/62 (3.2%)
Vaginal Bleeding	3/62 (4.8%)
Hematuria No Vaginal Bleeding	4/62 (6.5%)

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.