Ixabepilone to Treat Cervical Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00924066
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arm: 1
• Actual Duration (Months): 61
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Background:

• Ixabepilone is a member of the class of drugs called epothilones. These drugs interfere with the ability of cancer cells to replicate.

• Epothilones are similar to taxanes, another class of drugs, which includes the drug Taxol. Taxol is widely used to treat a variety of cancers.

• Ixabepilone can work in cells that are resistant to Taxol.

Objectives:

• To determine whether ixabepilone is effective for treating cervical cancer.

Eligibility:

• Women 18 years of age or older with cervical cancer.

Design:

• Patients receive ixabepilone intravenously (through a vein) over 60 minutes on the first 5 days of each 21-day treatment cycle. Their dosage may be adjusted according to how their bodies respond to the drug.

• The number of cycles each woman receives depends on her response to the treatment.

• Patients have CT (computed tomography) scans and other tests before starting treatment and then every other treatment cycle to determine the response of the tumor to ixabepilone.

• Patients who can undergo a tumor biopsy (surgical removal of a sample of tumor tissue) are asked to have a biopsy done before starting treatment with ixabepilone and again on the fourth or fifth day of treatment. This procedure is optional.

Condition or Disease	Intervention/Treatment	Phase
Cervical Carcinoma; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Carcinoma, Non-SquamousType	Drug: Ixempra (Ixabepilone (BMS-247550) )	Phase 2

Detailed Description

Background

• Ixabepilone (Ixempra (Trademark), BMS-247550, NSC 710428) is a semi-synthetic analog of the natural product epothilone B.

• The epothilones are a novel class of non-taxane microtubule-stabilizing agents obtained from the fermentation of the cellulose degrading myxobacteria, Sorangium cellulosum.

• Ixabepilone is active against cancer models that are naturally insensitive to paclitaxel or have developed resistance to paclitaxel, both in-vitro and in-vivo.

Objectives

Primary-

• Establish the efficacy of the investigational agent ixabepilone in patients with cervical carcinoma when administered as a daily one-hour infusion on days 1 to 5 every three weeks, as measured by overall response (PR (partial response) +CR (complete response)).

Secondary-

• Assess pharmacodynamic endpoints to determine the extent of tubulin polymerization and whether or not there has been activation of cellular death pathways distal to the target.

• Estimate progression-free survival and duration of response.

Eligibility

• Age greater than 18

• Histologic or cytologic confirmation of cervical carcinoma; either squamous cell or non-squamous consisting of cervical adenocarcinoma, cervical adenosquamous carcinoma or cervical carcinoma, non-squamous type.

Design

• Phase II study, open, non-randomized

• Ixabepilone will be administered at a dose of 6mg/m^2 daily on days 1 through 5, every three weeks.

• Restaging will be done every two cycles using RECIST (Response Evaluation Criteria in Solid Tumors)

• Planned maximum enrollment 76 persons

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of Ixabepilone (Ixempra [R], BMS-247550, NSC 710428), an Epothilone B Analog, in Cervical Cancer
• Actual Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Squamous and Nonsquamous participants Squamous cell carcinoma is a histologic subtype of cervical cancer. Squamous cell carcinoma of the cervix (80%) is much more common than adenocarcinoma of the cervix. Non squamous carcinoma is a histologic subtype of cervical cancer. It is the second most common form of cervical cancer; consists of adenocarcinoma, adenosquamous and non squamous (not otherwise specified) subtypes. All participants in both arms received ixabepilone 6 mg/m^2 x 5 days, each cycle.

Drug: Ixempra (Ixabepilone (BMS-247550) ); Participants received Ixabepilone 6mg/m^2 for a total of 30mg/m^2 inpatient or outpatient intravenously over an hour on the first five days of each 21 day cycle.; Other Names: BMS-247550

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Tumor Response (PR + CR) Per RECIST [Every 6 weeks, up to 15 months]

   Establish the efficacy of the investigational agent Ixabepilone in patients with cervical carcinoma per the Response Evaluation Criteria in Solid Tumors (RECIST) when Ixabepilone is administered as a daily 1 hour infusion on days 1-5 every 3 weeks. Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Not evaluable (NE) means the participant was not evaluable because there was not a scan available to compare to the baseline scan.

Secondary Outcome Measures

1. Number of Participants With Serious and Non-Serious Adverse Events [Date treatment consent signed to date off study, approximately 61 months]

   Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

Patients must fulfill all of the following criteria to be eligible for study admission:

1. Age greater than or equal to 18 years.

2. Histologic or cytologic confirmation of cervical carcinoma, squamous or non-squamous. Within the non-squamous cohort is adenocarcinoma and adenosquamous as well as non-squamous (not otherwise specified).

3. Subjects with unresectable recurrent cervical cancer are eligible.

4. Measurable disease that can be assessed using RECIST (Response Evaluation Criteria in Solid Tumors) criteria.

5. Performance Status ECOG (Eastern Cooperative Oncology Group) 0-2.

6. Life expectancy of 3 months or greater.

7. Suitable candidate for receiving planned therapy as evidenced by screening laboratory assessments of hematologic, renal, hepatic, and metabolic functions: platelet count greater than or equal to 75,000/mm^{3, absolute granulocyte count (AGC) greater than or equal to 1,000/mm}3, serum creatinine less than or equal to 1.6 or a measured creatinine clearance greater than or equal to 40 ml/min, SGPT (serum glutamic pyruvic transaminase) and SGOT (serum glutamic oxaloacetic transaminase) less than or equal to 2.5 times the NL (normal limit), and total bilirubin less than or equal to 1.5 times the NL (in patients with clinical evidence of Gilberts' disease, less than or equal to 3 times the NL).

Note: A diagnosis of Gilbert s disease will be made in the presence of (1) unconjugated hyperbilirubinemia noted on several occasions; (2) normal results from CBC (complete blood count) count, reticulocyte count, and blood smear; (3) normal liver function test results; and (4) an absence of other disease processes that can explain the unconjugated hyperbilirubinemia.

1. Greater than or equal to 4 weeks from prior radiation, intravenous chemotherapy or immunotherapy; greater than or equal to 6 weeks from prior nitrosourea; greater than or equal to 2 weeks from a prior phase 0 study .

2. No serious intercurrent medical illness.

3. The ability to understand and willingness to sign a written informed consent form, and to comply with the protocol.

4. Prior therapy with cisplatin or carboplatin is required.

EXCLUSION CRITERIA:

Patients with any of the following will be excluded from study entry:

1. Pregnant or nursing women are not eligible; neither are women of childbearing potential unless using effective contraception as determined by the patients physician.

2. Patients with a history of CNS (central nervous system) metastases, because symptoms/signs of progressive disease may be confused with drug-related toxicities, unless control has been achieved with either radiation or surgical resection at least three months prior to enrollment on study.

3. Patients who are poor medical risk because of other non malignant systemic disease or active, uncontrolled infection.

4. Human Immunodeficiency Virus (HIV) positive patients will be considered for eligibility, as long as they are not receiving antiretroviral drugs with strong CYP3A4 (cytochrome P450 3A4) inhibitory activity.

5. Prior craniospinal radiation, or total body irradiation (TBI).

6. Patients receiving other investigational drugs, or strong CYP3A3 inhibitors (see Section 3.6 for details) that cannot be discontinued or substituted.

7. CTCAE (Common Terminology Criteria for Adverse Events) Grade 2 or greater motor or sensory neuropathy.

8. Known prior severe hypersensitivity reactions to agents containing Cremophor (Trademark) EL.

9. Women with localized disease who are potentially curable through surgical resection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Antonio T Fojo, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 4, 2013
• Informed Consent Form - Feb 16, 2012

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Alfsen GC, Kristensen GB, Skovlund E, Pettersen EO, Abeler VM. Histologic subtype has minor importance for overall survival in patients with adenocarcinoma of the uterine cervix: a population-based study of prognostic factors in 505 patients with nonsquamous cell carcinomas of the cervix. Cancer. 2001 Nov 1;92(9):2471-83.
• Levêque J, Laurent JF, Burtin F, Foucher F, Goyat F, Grall JY, Meunier B. Prognostic factors of the uterine cervix adenocarcinoma. Eur J Obstet Gynecol Reprod Biol. 1998 Oct;80(2):209-14.
• Parkin DM, Läärä E, Muir CS. Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer. 1988 Feb 15;41(2):184-97.

• Responsible Party: Antonio Fojo, M.D., Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00924066
• Other Study ID Numbers: 090037; 09-C-0037; NCT00798928
• First Posted: Jun 18, 2009
• Last Update Posted: Nov 21, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Antonio Fojo, M.D., Principal Investigator, National Cancer Institute (NCI): Ixabepilone; BMS-247550; Ixempra; Cervical Cancer; Epothilone
• Additional relevant MeSH terms: Carcinoma; Uterine Cervical Neoplasms; Carcinoma, Adenosquamous; Epothilones

Study Results

Participant Flow

Arm/Group Title	Squamous and Nonsquamous Participants
Arm/Group Description	Squamous cell carcinoma is a histologic subtype of cervical cancer. Squamous cell carcinoma of the cervix (80%) is much more common than adenocarcinoma of the cervix. Non squamous carcinoma is a histologic subtype of cervical cancer. It is the second most common form of cervical cancer; consists of adenocarcinoma, adenosquamous and non squamous (not otherwise specified) subtypes. All participants in both arms received ixabepilone 6 mg/m^2 x 5 days, each cycle.
Period Title: Overall Study
STARTED	41
COMPLETED	41
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Squamous and Nonsquamous Participants
Arm/Group Description	Squamous cell carcinoma is a histologic subtype of cervical cancer. Squamous cell carcinoma of the cervix (80%) is much more common than adenocarcinoma of the cervix. Non squamous carcinoma is a histologic subtype of cervical cancer. It is the second most common form of cervical cancer; consists of adenocarcinoma, adenosquamous and non squamous (not otherwise specified) subtypes. All participants in both arms received ixabepilone 6 mg/m^2 x 5 days, each cycle.
Overall Participants	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.79 (9.17)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	40 97.6%
>=65 years	1 2.4%
Sex: Female, Male (Count of Participants)
Female	41 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 7.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 9.8%
White	34 82.9%
More than one race	0 0%
Unknown or Not Reported	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 7.3%
Not Hispanic or Latino	37 90.2%
Unknown or Not Reported	1 2.4%
Region of Enrollment (Count of Participants)
United States	41 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Tumor Response (PR + CR) Per RECIST
Description	Establish the efficacy of the investigational agent Ixabepilone in patients with cervical carcinoma per the Response Evaluation Criteria in Solid Tumors (RECIST) when Ixabepilone is administered as a daily 1 hour infusion on days 1-5 every 3 weeks. Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Not evaluable (NE) means the participant was not evaluable because there was not a scan available to compare to the baseline scan.
Time Frame	Every 6 weeks, up to 15 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Squamous and Nonsquamous Participants
Arm/Group Description	Squamous cell carcinoma is a histologic subtype of cervical cancer. Squamous cell carcinoma of the cervix (80%) is much more common than adenocarcinoma of the cervix. Non squamous carcinoma is a histologic subtype of cervical cancer. It is the second most common form of cervical cancer; consists of adenocarcinoma, adenosquamous and non squamous (not otherwise specified) subtypes. All participants in both arms received ixabepilone 6 mg/m^2 x 5 days, each cycle.
Measure Participants	41
Not Evaluable (only 1 cycle)	2 4.9%
Progressive Disease	25 61%
Stable Disease	10 24.4%
Partial Response	4 9.8%
Complete Response	0 0%

2. Secondary Outcome

Title	Number of Participants With Serious and Non-Serious Adverse Events
Description	Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame	Date treatment consent signed to date off study, approximately 61 months

Outcome Measure Data

Analysis Population Description

Adverse events are grouped together because the histology cohort has no bearing on the adverse events.

Arm/Group Title	Squamous and Nonsquamous Participants
Arm/Group Description	Squamous cell carcinoma is a histologic subtype of cervical cancer. Squamous cell carcinoma of the cervix (80%) is much more common than adenocarcinoma of the cervix. Non squamous carcinoma is a histologic subtype of cervical cancer. It is the second most common form of cervical cancer; consists of adenocarcinoma, adenosquamous and non squamous (not otherwise specified) subtypes. All participants in both arms received ixabepilone 6 mg/m^2 x 5 days, each cycle.
Measure Participants	41
Count of Participants [Participants]	41 100%

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately 61 months.
Arm/Group Title	Adverse Events for Squamous and Non-squamous Participants
Arm/Group Description	Squamous cell carcinoma is a histologic subtype of cervical cancer. Squamous cell carcinoma of the cervix (80%) is much more common than adenocarcinoma of the cervix. Non squamous carcinoma is a histologic subtype of cervical cancer. It is the second most common form of cervical cancer; consists of adenocarcinoma, adenosquamous and non squamous (not otherwise specified) subtypes. All participants in both arms received ixabepilone 6 mg/m^2 x 5 days, each cycle.
All Cause Mortality
	Adverse Events for Squamous and Non-squamous Participants
	Affected / at Risk (%)	# Events
Total	2/41 (4.9%)
Serious Adverse Events
	Adverse Events for Squamous and Non-squamous Participants
	Affected / at Risk (%)	# Events
Total	18/41 (43.9%)
Blood and lymphatic system disorders
Anemia	2/41 (4.9%)	2
Gastrointestinal disorders
Abdominal pain	1/41 (2.4%)	1
Colonic fistula	1/41 (2.4%)	1
Colonic obstruction	1/41 (2.4%)	1
Duodenal obstruction	1/41 (2.4%)	1
Enterocolitis infectious	1/41 (2.4%)	1
Ileal fistula	1/41 (2.4%)	1
Ileal obstruction	1/41 (2.4%)	1
Ileus	2/41 (4.9%)	2
Nausea	2/41 (4.9%)	2
Small intestinal obstruction	1/41 (2.4%)	1
Vomiting	2/41 (4.9%)	2
General disorders
Death NOS	2/41 (4.9%)	2
Fever	3/41 (7.3%)	3
Pain	1/41 (2.4%)	2
Infections and infestations
Catheter related infection	1/41 (2.4%)	1
Joint infection	1/41 (2.4%)	1
Phlebitis infective	1/41 (2.4%)	1
Investigations
Alanine aminotransferase increased	1/41 (2.4%)	1
Alkaline phosphatase increased	1/41 (2.4%)	1
Aspartate aminotransferase increased	1/41 (2.4%)	1
Metabolism and nutrition disorders
Dehydration	2/41 (4.9%)	2
Hypoalbuminemia	1/41 (2.4%)	1
Musculoskeletal and connective tissue disorders
Joint effusion	1/41 (2.4%)	1
Musculoskeletal and connective tissue disorder - Other, specify	1/41 (2.4%)	1
Nervous system disorders
Depressed level of consciousness	1/41 (2.4%)	1
Intracranial hemorrhage	1/41 (2.4%)	1
Psychiatric disorders
Depression	1/41 (2.4%)	1
Renal and urinary disorders
Cystitis noninfective	1/41 (2.4%)	1
Hematuria	1/41 (2.4%)	1
Urinary fistula	1/41 (2.4%)	1
Urinary retention	1/41 (2.4%)	1
Urinary tract obstruction	3/41 (7.3%)	3
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/41 (2.4%)	1
Pneumothorax	1/41 (2.4%)	1
Vascular disorders
Thromboembolic event	2/41 (4.9%)	2
Other (Not Including Serious) Adverse Events
	Adverse Events for Squamous and Non-squamous Participants
	Affected / at Risk (%)	# Events
Total	41/41 (100%)
Blood and lymphatic system disorders
Anemia	41/41 (100%)	256
Cardiac disorders
Sinus bradycardia	1/41 (2.4%)	2
Sinus tachycardia	2/41 (4.9%)	2
Ear and labyrinth disorders
Tinnitus	1/41 (2.4%)	1
Eye disorders
Blurred vision	1/41 (2.4%)	2
Flashing lights	1/41 (2.4%)	1
Optic nerve disorder	1/41 (2.4%)	1
Gastrointestinal disorders
Abdominal distension	1/41 (2.4%)	1
Abdominal pain	8/41 (19.5%)	10
Colonic fistula	1/41 (2.4%)	2
Colonic hemorrhage	1/41 (2.4%)	1
Constipation	14/41 (34.1%)	18
Dental caries	1/41 (2.4%)	1
Diarrhea	13/41 (31.7%)	21
Duodenal obstruction	1/41 (2.4%)	1
Hemorrhoids	1/41 (2.4%)	1
Nausea	25/41 (61%)	46
Oral hemorrhage	1/41 (2.4%)	1
Rectal fistula	1/41 (2.4%)	1
Rectal hemorrhage	2/41 (4.9%)	2
Rectal mucositis	2/41 (4.9%)	2
Rectal pain	1/41 (2.4%)	1
Rectal ulcer	1/41 (2.4%)	1
Vomiting	18/41 (43.9%)	32
General disorders
Chills	3/41 (7.3%)	3
Edema limbs	9/41 (22%)	12
Edema trunk	2/41 (4.9%)	4
Fatigue	23/41 (56.1%)	46
Fever	8/41 (19.5%)	14
Gait disturbance	1/41 (2.4%)	1
Infusion related reaction	2/41 (4.9%)	2
Mucositis oral	6/41 (14.6%)	6
Non-cardiac chest pain	1/41 (2.4%)	1
Pain	3/41 (7.3%)	3
Immune system disorders
Allergic reaction	3/41 (7.3%)	3
Allergic rhinitis	2/41 (4.9%)	2
Infections and infestations
Infections and infestations - Other, specify (Toe nail W normal ANC)	2/41 (4.9%)	2
Mucosal infection	3/41 (7.3%)	3
Sinusitis	1/41 (2.4%)	1
Skin infection	1/41 (2.4%)	1
Urinary tract infection	8/41 (19.5%)	8
Injury, poisoning and procedural complications
Vascular access complication	1/41 (2.4%)	1
Investigations
Activated partial thromboplastin time prolonged	1/41 (2.4%)	1
Alanine aminotransferase increased	12/41 (29.3%)	26
Alkaline phosphatase increased	21/41 (51.2%)	44
Aspartate aminotransferase increased	14/41 (34.1%)	27
Blood bilirubin increased	5/41 (12.2%)	10
CPK increased	4/41 (9.8%)	5
Creatinine increased	12/41 (29.3%)	31
Investigations - Other, specify	4/41 (9.8%)	6
Lymphocyte count decreased	41/41 (100%)	304
Neutrophil count decreased	8/41 (19.5%)	12
Platelet count decreased	25/41 (61%)	83
Weight loss	5/41 (12.2%)	5
White blood cell decreased	18/41 (43.9%)	75
Metabolism and nutrition disorders
Acidosis	1/41 (2.4%)	1
Anorexia	19/41 (46.3%)	26
Dehydration	2/41 (4.9%)	3
Hypercalcemia	15/41 (36.6%)	35
Hyperglycemia	5/41 (12.2%)	6
Hyperkalemia	3/41 (7.3%)	3
Hypermagnesemia	5/41 (12.2%)	9
Hypernatremia	3/41 (7.3%)	4
Hyperuricemia	12/41 (29.3%)	24
Hypoalbuminemia	31/41 (75.6%)	92
Hypocalcemia	12/41 (29.3%)	18
Hypokalemia	18/41 (43.9%)	41
Hypomagnesemia	25/41 (61%)	79
Hyponatremia	22/41 (53.7%)	48
Hypophosphatemia	13/41 (31.7%)	32
Musculoskeletal and connective tissue disorders
Arthralgia	7/41 (17.1%)	11
Back pain	4/41 (9.8%)	6
Bone pain	2/41 (4.9%)	2
Flank pain	1/41 (2.4%)	1
Muscle weakness lower limb	1/41 (2.4%)	1
Myalgia	5/41 (12.2%)	7
Neck pain	1/41 (2.4%)	1
Pain in extremity	2/41 (4.9%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	5/41 (12.2%)	5
Nervous system disorders
Depressed level of consciousness	1/41 (2.4%)	1
Dizziness	6/41 (14.6%)	6
Dysgeusia	3/41 (7.3%)	4
Headache	5/41 (12.2%)	6
Neuralgia	4/41 (9.8%)	5
Peripheral motor neuropathy	2/41 (4.9%)	3
Peripheral sensory neuropathy	9/41 (22%)	14
Somnolence	1/41 (2.4%)	1
Syncope	1/41 (2.4%)	1
Psychiatric disorders
Confusion	1/41 (2.4%)	1
Depression	4/41 (9.8%)	4
Insomnia	1/41 (2.4%)	3
Renal and urinary disorders
Cystitis noninfective	2/41 (4.9%)	2
Hematuria	5/41 (12.2%)	5
Proteinuria	1/41 (2.4%)	1
Urinary fistula	1/41 (2.4%)	2
Urinary frequency	2/41 (4.9%)	2
Urinary incontinence	2/41 (4.9%)	2
Urinary retention	1/41 (2.4%)	1
Urinary tract obstruction	2/41 (4.9%)	2
Urinary tract pain	3/41 (7.3%)	5
Urinary urgency	1/41 (2.4%)	1
Reproductive system and breast disorders
Pelvic pain	4/41 (9.8%)	4
Vaginal hemorrhage	2/41 (4.9%)	2
Vaginal inflammation	1/41 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/41 (7.3%)	4
Dyspnea	7/41 (17.1%)	10
Epistaxis	1/41 (2.4%)	1
Hypoxia	1/41 (2.4%)	4
Pleural effusion	2/41 (4.9%)	2
Pneumonitis	1/41 (2.4%)	1
Skin and subcutaneous tissue disorders
Alopecia	11/41 (26.8%)	14
Hyperhidrosis	2/41 (4.9%)	3
Nail loss	2/41 (4.9%)	2
Pruritus	1/41 (2.4%)	1
Rash acneiform	2/41 (4.9%)	2
Surgical and medical procedures
Surgical and medical procedures - Other, specify	1/41 (2.4%)	1
Vascular disorders
Hypertension	3/41 (7.3%)	3
Hypotension	1/41 (2.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.