BMS 247550 to Treat Kidney Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00030992
• Collaborator: (none)
• Enrollment: 102
• Location: 1
• Arm: 1
• Duration (Months): 124
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This study will examine whether the experimental drug BMS 247550 (Ixabepilone) is an effective treatment for kidney cancer. BMS 247550 belongs to a class of drugs called epothilones that interfere with the ability of cancer cells to divide. In the way they kill cells, they are very similar to a class of compounds known as the taxanes, which include the drug Taxol. Other characteristics of the epothilones, however, enable them to work in cells that are resistant to Taxol.

Patients 18 years of age or older with kidney cancer that has not spread to the central nervous system (unless the brain tumor has remained stable for at least six months after surgical or radiation treatment) may be eligible for this study. Pregnant or nursing women may not participate. Candidates are screened with various tests that may include blood and urine tests, electrocardiogram (EKG), and chest x-ray. Computerized tomography (CT) scans or X-rays, and possibly nuclear medicine studies may be done to determine the extent of disease.

Participants receive BMS 247550 by a 1-hour infusion into a vein for 5 consecutive days (days 1, 2, 3, 4 and 5) of each 21-day treatment cycle. Patients must stay in the National Institutes of Health (NIH) area near Bethesda, Maryland, for 7 to 8 days during the first treatment cycle and for the 5 days of treatment in subsequent cycles. The total number of cycles will vary among patients, depending on their individual clinical situation. The drug dose may be increased gradually in subsequent cycles in patients who can tolerate such increases. In addition, participants undergo the following tests and procedures:

• Periodic physical examinations and frequent blood tests

• X-ray and other imaging studies to determine if the tumor is responding to the treatment.

• Tumor biopsies to confirm the diagnosis or spread of tumor and to examine the reaction of certain proteins in cancer cells to BMS 247550. Two biopsies will be done. For this procedure, a small piece of tumor tissue is withdrawn through a needle under local anesthetic.

Treatment will be stopped in patients whose tumor grows while receiving BMS 247550. Patients whose tumor disappears completely will be followed at NIH periodically for examinations and tests. Patients whose disease does not completely resolve or whose disease recurs may be advised of other appropriate research protocols at NIH or, if none are available, will be returned to the care of their local doctor.

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma	Drug: BMS-247550; Drug: Ranitidine; Drug: Diphenhydramine	Phase 2

Detailed Description

Background:

BMS-247550 (NSC 710428), (ixabepilone) 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.

BMS-247550 is active against cancer models that are naturally insensitive to paclitaxel or have developed resistance to paclitaxel, both in-vitro and in-vivo.

Objectives

Establish the efficacy of the investigational agent BMS-247550 in patients with renal cell carcinoma when administered as a one hour infusion on day 1 to 5 every 21 days.

Evaluate the plasma pharmacokinetics of BMS-247550.

Explore the pharmacodynamics of BMS-247550 using an assay that measures the amount of endogenous tubulin in peripheral blood mononuclear cells (PBMC) that exists in the polymerized versus the unpolymerized state.

Determine the extent to which pharmacodynamic changes are observed over a range of doses of BMS-247550.

Determine if cross-resistance to BMS-247550 exists in patients who have previously received sorafenib or sunitinib.

Eligibility:

Age greater than 18.

Pathological confirmation of renal cell carcinoma.

Prior chemotherapy including sorafenib and sunitinib is allowed.

Design:

Phase II study.

BMS-247550 will be administered on days 1 through 5, every 21 days.

Restaging will be done every two cycles.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of BMS-247550 (NSC 710428), an Epothilone B Analog, in Renal Cell Carcinoma
• Study Start Date: Feb 1, 2002
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BMS-247550 One hour infusion on five successive days (daily x 5) every three weeks. Starting dose of 6 mg/m^2/day for a total per cycle dose of 30 mg/m^2	Drug: BMS-247550; One hour infusion on five successive days (daily x 5) every three weeks. Starting dose of 6 mg/m^2/day for a total per cycle dose of 30 mg/m^2; Drug: Ranitidine; 50 mg 30-60 minutes prior to Ixabepilone (BMS-247550); Other Names: Zantac ; Drug: Diphenhydramine; 50 mg intravenously 30-60 minutes prior to Ixabepilone (BMS-247550); Other Names: Benadryl Diphenhist Diphedryl

Outcome Measures

Primary Outcome Measures

1. Response Rate [6 weeks]

   Response rate is the percentage of participants with a response assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is 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,progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions 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.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [10 years]

   Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• 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 renal cell carcinoma (clear cell, type I and type II papillary, chromophobe, collecting duct and medullary).

Patients should either:

1. have received interleukin-2 (IL-2);

2. have been evaluated for therapy with IL-2 and deemed to be ineligible; or (c) have been evaluated for therapy with IL-2 and refused treatment.

3. Measurable extent of disease.

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

5. Life expectancy of 3 months or greater.

6. 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 100,000/mL, absolute granulocyte count (AGC) greater than or equal to 1,500/mL, serum creatinine less than or equal to 1.6 or a measured creatinine clearance greater than or equal to 40 ml/min, serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5 x normal limit (NL), and total bilirubin less than or equal to 1.5 x NL (in patients with clinical evidence of Gilberts' disease, less than or equal to 3 x NL).

1. Greater than or equal to 4 weeks from prior cytotoxic chemotherapy, radiation or immunotherapy; greater than or equal to 2 weeks from prior targeted-therapy (cytostatic agents); such patients should have recovered from toxicity from the prior therapy.

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. Patients should either: (a) have received sorafenib and or sunitinib and had progressive disease while receiving the drug(s) or (b) been intolerant to the drugs(s), or (c) been evaluated for therapy with sorafenib and or sunitinib and deemed to be ineligible; or (d) have been evaluated for therapy with sorafenib and or sunitinib and refused treatment.

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 or men of childbearing potential unless using effective contraception as determined by the patient's physician.

2. Patients with a history of central nervous system (CNS) 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 six 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) seropositive patients. Patients infected with the HIV virus will be excluded from this trial because the effect of BMS-247550 on HIV replication and/or the immune system is unknown and may be potentially harmful.

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

6. Patients receiving other investigational drugs, or St. John's Wort (St. John's Wort can induce P450 and alter drug metabolism).

7. Common Toxicity Criteria (CTC) Grade 2 or greater motor or sensory neuropathy.

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

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: Tito Fojo, M.D., National Cancer Institute, National Institutes of Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Huizing MT, Misser VH, Pieters RC, ten Bokkel Huinink WW, Veenhof CH, Vermorken JB, Pinedo HM, Beijnen JH. Taxanes: a new class of antitumor agents. Cancer Invest. 1995;13(4):381-404. Review.
• Von Hoff DD. The taxoids: same roots, different drugs. Semin Oncol. 1997 Aug;24(4 Suppl 13):S13-3-S13-10. Review.
• Wilson L, Jordan MA. Microtubule dynamics: taking aim at a moving target. Chem Biol. 1995 Sep;2(9):569-73. Review.

• ClinicalTrials.gov Identifier: NCT00030992
• Other Study ID Numbers: 020130; 02-C-0130; NCT00033670
• First Posted: Feb 21, 2002
• Last Update Posted: Aug 20, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by , ,: Epothilone B; Ixabepilone; Renal Cell Carcinoma; Kidney Cancer
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Diphenhydramine; Promethazine; Ranitidine; Ranitidine bismuth citrate

Study Results

Participant Flow

Recruitment Details	102 participants were enrolled in this study.

Arm/Group Title	BMS-247550
Arm/Group Description	One hour infusion on five successive days (daily x 5) every three weeks. Starting dose of 6 mg/m^2/day for a total per cycle dose of 30 mg/m^2
Period Title: Overall Study
STARTED	102
COMPLETED	102
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	BMS-247550
Arm/Group Description	One hour infusion on five successive days (daily x 5) every three weeks. Starting dose of 6 mg/m^2/day for a total per cycle dose of 30 mg/m^2
Overall Participants	102
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	79 77.5%
>=65 years	23 22.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.21 (10.81)
Sex: Female, Male (Count of Participants)
Female	24 23.5%
Male	78 76.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 2%
Not Hispanic or Latino	100 98%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	84 82.4%
African American	12 11.8%
Asian	5 4.9%
Hispanic	1 1%
Region of Enrollment (participants) [Number]
United States	102 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Response rate is the percentage of participants with a response assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is 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,progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions 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.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BMS-247550
Arm/Group Description	One hour infusion on five successive days (daily x 5) every three weeks. Starting dose of 6 mg/m^2/day for a total per cycle dose of 30 mg/m^2
Measure Participants	102
Complete response	1 1%
Partial Response	9.4 9.2%
Progressive disease	12.6 12.4%
Stable disease	76.8 75.3%

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BMS-247550
Arm/Group Description	One hour infusion on five successive days (daily x 5) every three weeks. Starting dose of 6 mg/m^2/day for a total per cycle dose of 30 mg/m^2
Measure Participants	102
Number [Participants]	99 97.1%

Adverse Events

Time Frame	10 years
Arm/Group Title	BMS-247550
Arm/Group Description	One hour infusion on five successive days (daily x 5) every three weeks. Starting dose of 6 mg/m^2/day for a total per cycle dose of 30 mg/m^2
All Cause Mortality
	BMS-247550
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	BMS-247550
	Affected / at Risk (%)	# Events
Total	40/102 (39.2%)
Blood and lymphatic system disorders
Febrile neutropenia	2/102 (2%)	2
Hemoglobin (hgb)	4/102 (3.9%)	4
Hemorrhage/bleeding associated with surgery	1/102 (1%)	1
Cardiac disorders
Cardiac left ventricular function	1/102 (1%)	1
Cardiac troponin T (cTnT)	1/102 (1%)	1
Cardiac-ischemia/infarction	1/102 (1%)	1
Circulatory or cardiac-Other (hypertension)	1/102 (1%)	1
CNS cerebrovascular ischemia	1/102 (1%)	1
Pericardial effusion/pericarditis	1/102 (1%)	1
Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)	1/102 (1%)	1
Gastrointestinal disorders
Diarrhea (without colostomy)	5/102 (4.9%)	5
Dysphagia, esophagitis, odynophagia (painful swallowing)	1/102 (1%)	1
Melena/GI bleeding	1/102 (1%)	1
Nausea	3/102 (2.9%)	3
Vomiting	1/102 (1%)	1
General disorders
Edema	1/102 (1%)	1
Fatigue (lethargy, malaise, asthenia)	3/102 (2.9%)	3
Fever	8/102 (7.8%)	8
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/102 (1%)	1
Infections and infestations
Catheter-related infection	1/102 (1%)	1
Infection	3/102 (2.9%)	3
Infection with neutropenia	1/102 (1%)	1
Infection without neutropenia	7/102 (6.9%)	7
Infection, Other (other than fever with neutropenia)	2/102 (2%)	2
Stomatitis/pharyngitis (oral/pharyngeal mucositis) for BMT	3/102 (2.9%)	3
Investigations
Alkaline phosphatase	1/102 (1%)	1
CPK (creatine phosphokinase)	1/102 (1%)	1
Creatinine	2/102 (2%)	3
Hemoglobin increased	1/102 (1%)	1
Neutrophils/granulocytes (ANC/AGC)	5/102 (4.9%)	5
Platelet count decreased	1/102 (1%)	1
SGOT (AST)	1/102 (1%)	1
SGPT (ALT)	1/102 (1%)	1
Weight loss	1/102 (1%)	1
Metabolism and nutrition disorders
Dehydration	6/102 (5.9%)	6
Hyperkalemia	2/102 (2%)	2
Hypertriglyceridemia	1/102 (1%)	1
Hyperuricemia	2/102 (2%)	2
Hypoalbuminemia	1/102 (1%)	1
Hypocalcemia	1/102 (1%)	1
Hypokalemia	2/102 (2%)	2
Hypomagnesemia	1/102 (1%)	1
Hyponatremia	2/102 (2%)	2
Musculoskeletal and connective tissue disorders
Joint, muscle, or bone (osseous)-Other (fracture)	1/102 (1%)	2
Nervous system disorders
Neurologic-Other (autonomic neuropathy)	2/102 (2%)	2
Neuropathic pain	1/102 (1%)	2
Neuropathy-motor	1/102 (1%)	1
Pain-neuropathic	1/102 (1%)	1
Seizure(s)	1/102 (1%)	1
Syncope	3/102 (2.9%)	3
Vasovagal reaction	1/102 (1%)	1
Renal and urinary disorders
Acute kidney injury	1/102 (1%)	2
Hematuria (in the absence of vaginal bleeding)	3/102 (2.9%)	4
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome (ARDS)	1/102 (1%)	1
Dyspnea (shortness of breath)	6/102 (5.9%)	6
Hemoptysis	2/102 (2%)	2
Hypoxia	1/102 (1%)	1
Pleural effusion	1/102 (1%)	1
Pleural effusion (non-malignant)	1/102 (1%)	1
Pneumothorax	1/102 (1%)	1
Pulmonary-Other: malignant pleural effusion	1/102 (1%)	1
Voice changes/stridor/larynx	2/102 (2%)	2
Vascular disorders
Hypotension	6/102 (5.9%)	6
Thrombosis/embolism	1/102 (1%)	3
Other (Not Including Serious) Adverse Events
	BMS-247550
	Affected / at Risk (%)	# Events
Total	99/102 (97.1%)
Blood and lymphatic system disorders
Anemia	12/102 (11.8%)	52
Blood and lymphatic system disorders-Other, specify (bruising)	1/102 (1%)	1
Febrile neutropenia	1/102 (1%)	1
Hemoglobin (hgb)	65/102 (63.7%)	235
Hemorrhage/bleeding associated with surgery	1/102 (1%)	1
Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia	1/102 (1%)	1
Transfusion:pRBCs	2/102 (2%)	3
Cardiac disorders
Cardiac-ischemia/infarction	1/102 (1%)	1
Circulatory or cardiac-Other (edema)	2/102 (2%)	2
Palpitation	1/102 (1%)	1
Sinus tachycardia	1/102 (1%)	1
Ear and labyrinth disorders
Ear and labyrinth disorders-Other, specify (tinnitus)	1/102 (1%)	1
External auditory canal	1/102 (1%)	1
Middle ear/hearing	2/102 (2%)	2
Eye disorders
Blurred vision	1/102 (1%)	1
Conjunctivitis	1/102 (1%)	1
Dry eye	1/102 (1%)	1
Eye disorders-Other, specify (blepharitis)	2/102 (2%)	2
Ocular-Other (blurred vision)	1/102 (1%)	1
Tearing (watery eyes)	3/102 (2.9%)	4
Vision-blurred vision	1/102 (1%)	1
Vision-flashing lights/floaters	1/102 (1%)	1
Gastrointestinal disorders
Abdominal pain	1/102 (1%)	1
Abdominal pain or cramping	12/102 (11.8%)	19
Constipation	30/102 (29.4%)	40
Depressed level of consciousness	1/102 (1%)	1
Diarrhea	4/102 (3.9%)	4
Diarrhea (without colostomy)	42/102 (41.2%)	95
Dyspepsia/heartburn	7/102 (6.9%)	7
Gastritis	2/102 (2%)	2
GI-Other (bloating)	2/102 (2%)	2
Nausea	48/102 (47.1%)	132
Salivary gland changes	1/102 (1%)	1
Vomiting	37/102 (36.3%)	66
General disorders
Fatigue	13/102 (12.7%)	32
Chest pain (non-cardiac and non-pleuritic)	7/102 (6.9%)	9
Chills	2/102 (2%)	2
Edema	14/102 (13.7%)	19
Fatigue (lethargy, malaise, asthenia)	73/102 (71.6%)	220
Fever	2/102 (2%)	2
Fever (in absence of neutropenia, where neutropenia is defined as AGC<1.0x109/L)	30/102 (29.4%)	35
Pain	2/102 (2%)	2
Pain-Other (dysethesia)	17/102 (16.7%)	23
Rigors, chills	9/102 (8.8%)	10
Hepatobiliary disorders
Bilirubin	6/102 (5.9%)	10
Blood bilirubin increased	4/102 (3.9%)	8
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	12/102 (11.8%)	16
Allergic rhinitis	1/102 (1%)	1
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	15/102 (14.7%)	19
Infections and infestations
Catheter-related infection	3/102 (2.9%)	3
Infection without neutropenia	30/102 (29.4%)	41
Infection, Other (skin)	8/102 (7.8%)	8
Infections and infestations-Other, specify (skin)	4/102 (3.9%)	5
Stomatitis/pharyngitis (oral/pharyngeal mucositis)	10/102 (9.8%)	10
Stomatitis/pharyngitis (oral/pharyngeal mucositis) for BMT	9/102 (8.8%)	10
Injury, poisoning and procedural complications
Bruising (in absence of grade 3 or 4 thrombocytopenia)	1/102 (1%)	1
Postoperative hemorrhage	1/102 (1%)	1
Wound dehiscence	1/102 (1%)	1
Wound-infectious	1/102 (1%)	1
Wound-non-infectious	1/102 (1%)	1
Investigations
Activated partial thromboplastin time prolonged	4/102 (3.9%)	12
Alanine aminotransferase increased	3/102 (2.9%)	5
Alkaline phosphokinase	24/102 (23.5%)	33
Alkaline phosphokinase increased	4/102 (3.9%)	6
Allergy-Other (rhinitis)	1/102 (1%)	1
Amylase	1/102 (1%)	2
Aspartate aminotransferase increased	6/102 (5.9%)	13
Cardiac troponin I increased	1/102 (1%)	1
Cholesterol high	1/102 (1%)	1
CPK (creatine phosphokinase)	4/102 (3.9%)	5
CPK increased	2/102 (2%)	4
Creatinine	15/102 (14.7%)	21
Creatinine increased	5/102 (4.9%)	14
Hemoglobin increased	1/102 (1%)	10
Hypercholesterolemia	2/102 (2%)	2
INR increased	4/102 (3.9%)	6
Leukocytes (total WBC)	34/102 (33.3%)	96
Lymphocyte count decreased	7/102 (6.9%)	30
Lymphocyte count increased	1/102 (1%)	1
Neutrophil count decreased	2/102 (2%)	2
Neutrophils/granulocytes (ANC/AGC)	46/102 (45.1%)	142
Partial thromboplastin time (PTT)	10/102 (9.8%)	14
Platelet count decreased	3/102 (2.9%)	6
Platelets	27/102 (26.5%)	72
SGOT (AST)	29/102 (28.4%)	48
SGPT (ALT)	19/102 (18.6%)	31
Weight loss	17/102 (16.7%)	20
White blood cell decreased	5/102 (4.9%)	15
Metabolism and nutrition disorders
Acidosis	3/102 (2.9%)	3
Anorexia	56/102 (54.9%)	88
Dehydration	16/102 (15.7%)	22
Hypercalcemia	12/102 (11.8%)	18
Hyperglycemia	17/102 (16.7%)	28
Hyperkalemia	15/102 (14.7%)	24
Hypermagnesemia	6/102 (5.9%)	9
Hypernatremia	1/102 (1%)	1
Hypertriglyceridemia	10/102 (9.8%)	13
Hyperuricemia	9/102 (8.8%)	13
Hypoalbuminemia	62/102 (60.8%)	113
Hypocalcemia	12/102 (11.8%)	22
Hypokalemia	9/102 (8.8%)	15
Hypomagnesemia	19/102 (18.6%)	45
Hyponatremia	18/102 (17.6%)	37
Hypophosphatemia	8/102 (7.8%)	10
Musculoskeletal and connective tissue disorders
Arthralgia	2/102 (2%)	2
Arthralgia (joint pain)	31/102 (30.4%)	49
Bone pain	1/102 (1%)	1
Generalized muscle weakness	1/102 (1%)	1
Joint, muscle, or bone (osseous)-Other (myalgia)	4/102 (3.9%)	4
Muscle weakness (not due to neuropathy)	4/102 (3.9%)	5
Myalgia (muscle ache)	14/102 (13.7%)	21
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	3/102 (2.9%)	6
Tumor pain (onset or exacerbation of tumor pain due to treatment)	1/102 (1%)	1
Nervous system disorders
Neuropathy-motor	2/102 (2%)	2
Dizziness	2/102 (2%)	2
Dizziness/lightheadedness	8/102 (7.8%)	9
Dysgeusia	2/102 (2%)	2
Extrapyramidal/involuntary movement/restlessness	3/102 (2.9%)	4
Headache	15/102 (14.7%)	21
Leukoencephalopathy	1/102 (1%)	1
Memory loss	1/102 (1%)	1
Nervous system disorders-Other, specify (vasovagal)	1/102 (1%)	1
Neurologic-Other (dizziness)	3/102 (2.9%)	3
Neuropathic pain	6/102 (5.9%)	9
Neuropathy-sensory	50/102 (49%)	88
Peripheral sensory neuropathy	5/102 (4.9%)	5
Sense of smell	1/102 (1%)	1
Syncope	2/102 (2%)	2
Taste disturbance (dysgeusia)	40/102 (39.2%)	86
Tremor	2/102 (2%)	3
Psychiatric disorders
Confusion	1/102 (1%)	1
Depression	1/102 (1%)	1
Insomnia	13/102 (12.7%)	15
Mood alteration-anxiety agitation	3/102 (2.9%)	3
Mood alteration-depression	8/102 (7.8%)	10
Mood alteration-euphoria	1/102 (1%)	1
Renal and urinary disorders
Dysuria (painful urination)	1/102 (1%)	1
Hematuria	1/102 (1%)	1
Hematuria (in the absence of vaginal bleeding)	6/102 (5.9%)	9
Incontinence	1/102 (1%)	1
Proteinuria	11/102 (10.8%)	11
Renal/GU-Other (urgency)	1/102 (1%)	1
Ureteral obstruction	1/102 (1%)	1
Urinary frequency	1/102 (1%)	1
Urinary frequency/urgency	1/102 (1%)	1
Urinary retention	1/102 (1%)	1
Reproductive system and breast disorders
Vaginal bleeding	2/102 (2%)	3
Vaginal dryness	1/102 (1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	29/102 (28.4%)	39
Dyspnea	5/102 (4.9%)	8
Epistaxis	6/102 (5.9%)	9
Hemoptysis	5/102 (4.9%)	6
Pleural effusion	1/102 (1%)	2
Pleuritic pain	2/102 (2%)	2
Postnasal drip	1/102 (1%)	1
Pericardial effusion/pericarditis	2/102 (2%)	2
Voice changes/stridor/larynx	1/102 (1%)	2
Dyspnea (shortness of breath)	19/102 (18.6%)	22
Skin and subcutaneous tissue disorders
Alopecia	61/102 (59.8%)	76
Dermatitis, focal	1/102 (1%)	1
Dry skin	3/102 (2.9%)	3
Erythema multiforme	1/102 (1%)	1
Nail changes	37/102 (36.3%)	47
Nail discoloration	1/102 (1%)	1
Nail loss	1/102 (1%)	2
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	1/102 (1%)	1
Pruritis	2/102 (2%)	2
Rash/desquamation	12/102 (11.8%)	13
Skin-Other (dry skin)	2/102 (2%)	2
Sweating	5/102 (4.9%)	6
Vascular disorders
Flushing	1/102 (1%)	1
Hot flashes/flashes	1/102 (1%)	1
Hypotension	6/102 (5.9%)	7
Phlebitis (superficial)	4/102 (3.9%)	4
Prothrombin time (PT)	5/102 (4.9%)	5
Thromboembolic event	1/102 (1%)	1
Thrombosis/embolism	1/102 (1%)	1
Hypertension	4/102 (3.9%)	4

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.