Vitamin E in Preventing Peripheral Neuropathy Caused by Chemotherapy in Patients Receiving Chemotherapy for Cancer

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00363129
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 207
• Locations: 69
• Arms: 2
• Duration (Months): 92
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Vitamin E may prevent peripheral neuropathy caused by chemotherapy in patients with cancer. It is not yet known whether vitamin E is more effective than a placebo in preventing peripheral neuropathy caused by chemotherapy in patients receiving chemotherapy for cancer.

PURPOSE: This randomized phase III trial is studying vitamin E to see how well it works compared with placebo in preventing peripheral neuropathy caused by chemotherapy in patients receiving chemotherapy for cancer.

Condition or Disease	Intervention/Treatment	Phase
Neurotoxicity; Unspecified Adult Solid Tumor, Protocol Specific	Dietary Supplement: vitamin E; Other: placebo	Phase 3

Detailed Description

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to type of chemotherapy (taxane vs cisplatin vs carboplatin vs oxaliplatin vs combination), age (≤ 50 years vs > 50 years), and gender. Patients are randomized to 1 of 2 treatment arms.

OBJECTIVES:

Primary

• Compare the incidence of chemotherapy-induced sensory peripheral neuropathy ≥ grade 2 in patients undergoing curative neurotoxic chemotherapy for cancer treated with vitamin E vs placebo.

Secondary

• Compare the proportion of patients requiring dose reductions of chemotherapy secondary to sensory peripheral neuropathy.

• Compare the proportion of patients stopping chemotherapy before treatment is complete secondary to sensory peripheral neuropathy.

• Assess the toxicity of vitamin E in these patients.

After completion of study treatment, patients are followed at 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 207 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: The Use of Vitamin E for Prevention of Chemotherapy Induced Peripheral Neuropathy: A Phase III Double-Blind Placebo Controlled Study
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral vitamin E twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.	Dietary Supplement: vitamin E; Given orally
Placebo Comparator: Arm II Patients receive oral placebo twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.	Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Chemotherapy-induced Sensory Peripheral Neuropathy ≥ Grade 2 [6 months post completion of chemotherapy treatment]

   The chemotherapy-induced sensory peripheral neuropathy utilized the sensory neuropathy item from the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grading: Grade 0=none; grade 1=loss of deep tendon reflexes or paresthesia, including tingling, but not interfering with function; grade 2=objective sensory alteration or paresthesia, including tingling, interfering with function, but not with activities of daily living; grade 3=sensory alteration or paresthesia interfering with activities of daily living; grade 4=permanent sensory losses that are disabling; and grade 5=death.

Secondary Outcome Measures

1. Percentage of Patients Requiring Dose Reductions of Chemotherapy Due to Sensory Peripheral Neuropathy [6 months post completion of chemotherapy treatment]

2. Percentage of Patients Stopping Chemotherapy Before Treatment is Complete Due to Sensory Peripheral Neuropathy [6 months post completion of chemotherapy treatment]

3. Time to Onset of Sensory Peripheral Neuropathy ≥ Grade 2 [6 months post completion of chemotherapy treatment]

   Time to onset of sensory peripheral neuropathy was calculated using incidences of the adverse event while the patient was receiving chemotherapy.

4. Duration of Sensory Peripheral Neuropathy ≥ Grade 2 [6 months post completion of chemotherapy treatment]

   Duration of sensory peripheral neuropathy is the time from onset of grade 2+ neuropathy until the neuropathy is resolved to grade 1 or less during chemotherapy treatment.

Eligibility Criteria

Criteria

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

Required Characteristics:

1. Scheduled to undergo curative-intent adjuvant treatment with neurotoxic chemotherapy. Patients must have had his/her tumor removed, but may have microscopic residual disease, or residual margin involvement and still be eligible.

The patient's chemotherapy regimen must include one or more of the following neurotoxic chemotherapeutic agents: taxanes (paclitaxel, docetaxel); platinum compounds (cisplatin, carboplatin, oxaliplatin)-(oxaliplatin patients should preferentially be enrolled in protocol N04C7 while it is available).

1. ≥ 18 years of age

2. Ability to sign informed consent and understand the nature of a placebo-controlled trial

3. ECOG Performance Status (PS) of 0, 1, or 2 e.g.

4. Ability to complete questionnaire(s) by themselves or with assistance

5. Life expectancy ≥ 6 months

Contraindications:

1. Undergoing chemotherapy for palliative care

2. Pre-existing history of peripheral neuropathy due to any cause (diabetes, alcohol, toxin, hereditary, etc).

3. Prior treatment with neurotoxic chemotherapy (exception: Patient started neurotoxic chemotherapy ≤ 4 days of starting vitamin E on this study and has not been treated previously with other neurotoxic chemotherapy agents).

4. Taking regular opioid-containing medications. (Exception: opioids, given for the short term treatment of chemotherapy-induced myalgias or arthralgias caused by taxanes are permitted.)

5. Concurrent treatment with anticonvulsants, tricyclic antidepressants, or other neuropathic pain medications agents such as carbamazepine, phenytoin, valproic acid, gabapentin, lamotrigine, topical lidocaine patch, capsaicin cream, etc.

6. History of coronary artery disease (i.e. MI, PTCA, or CABG ≤ 5 years or diagnosis of congestive heart failure of any NY heart class I-IV) Valve replacements are permitted as long as patient has fully recovered from the surgery.

7. Other medical conditions, which in the opinion of the treating physician/allied health professional would make this protocol unreasonably hazardous for the patient.

8. Vitamin E supplementation for any reason ≤ 7 days prior to randomization. (Exception:

one multivitamin per day that contains ≤ 100 IU [mg] of Vitamin E, will be permitted.)

1. Any of the following: pregnant women, nursing women and men or women of childbearing potential who are unwilling to employ adequate contraception

2. Taking anticoagulant medication (i.e. coumadin, low molecular weight heparin (LMWH), or platelet aggregation inhibitors such as clopidgrel or aspirin) with the exception that 1 mg/day of coumadin for central line maintenance is allowed.

3. Diagnosed diabetes requiring insulin or oral hypoglycemic medications

4. Head or neck cancers

5. Scheduled to undergo radiation therapy while on study

6. History of hemorrhagic stroke

7. Patients receiving neo-adjuvant therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
2	Graham Hospital	Canton	Illinois	United States	61520
3	Memorial Hospital	Carthage	Illinois	United States	62321
4	Eureka Community Hospital	Eureka	Illinois	United States	61530
5	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
6	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
7	Mason District Hospital	Havana	Illinois	United States	62644
8	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
9	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
10	Kewanee Hospital	Kewanee	Illinois	United States	61443
11	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
12	Community Cancer Center	Normal	Illinois	United States	61761
13	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
14	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
15	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
16	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
17	Perry Memorial Hospital	Princeton	Illinois	United States	61356
18	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
19	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
20	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
21	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
22	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
23	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
24	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
25	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
26	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
27	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
28	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
29	Foote Memorial Hospital	Jackson	Michigan	United States	49201
30	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
31	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
32	St. John Macomb Hospital	Warren	Michigan	United States	48093
33	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
34	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
35	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
36	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
37	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
38	Meeker County Memorial Hospital	Lichfield	Minnesota	United States	55355
39	Immanuel St. Joseph's	Mankato	Minnesota	United States	56002
40	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
41	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
42	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
43	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
44	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
45	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
46	HealthEast Cancer Care at St. Joseph's Hospital	St Paul	Minnesota	United States	55102
47	United Hospital	St. Paul	Minnesota	United States	55102
48	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
49	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
50	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
51	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
52	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
53	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
54	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
55	CCOP - Columbus	Columbus	Ohio	United States	43215
56	Grant Riverside Cancer Services	Columbus	Ohio	United States	43215
57	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
58	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
59	Grady Memorial Hospital	Delaware	Ohio	United States	43015
60	Fairfield Medical Center	Lancaster	Ohio	United States	43130
61	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
62	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
63	Mercy Medical Center	Springfield	Ohio	United States	45504
64	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
65	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
66	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
67	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
68	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
69	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Lisa Kottschade, RN, MSN, CNP, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00363129
• Other Study ID Numbers: NCCTG-N05C3; NCI-2011-01712; CDR0000491071
• First Posted: Aug 15, 2006
• Last Update Posted: Jul 6, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Alliance for Clinical Trials in Oncology: neurotoxicity; unspecified adult solid tumor, protocol specific
• Additional relevant MeSH terms: Peripheral Nervous System Diseases; Neurotoxicity Syndromes; Vitamin E

Study Results

Participant Flow

Recruitment Details	Two-hundred and seven (207) participants were recruited between December 2006 and December 2007 from 23 North Central Cancer Treatment Group (NCCTG) member sites.
Pre-assignment Detail	There were a total of 11 cancellations (4 Vitamin E, 7 Placebo), 1 major violation on Placebo and 7 ineligible (3 Vitamin E and 4 Placebo) participants. Of these, 18 participants of cancellations/ineligible were excluded from all analysis.

Arm/Group Title	Vitamin E	Placebo
Arm/Group Description	Patients receive oral vitamin E twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.	Patients receive oral placebo twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.
Period Title: Overall Study
STARTED	96	93
COMPLETED	67	60
NOT COMPLETED	29	33

Baseline Characteristics

Arm/Group Title	Vitamin E	Placebo	Total
Arm/Group Description	Patients receive oral vitamin E twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.	Patients receive oral placebo twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.	Total of all reporting groups
Overall Participants	96	93	189
Age, Customized (participants) [Number]
<=50 years	40 41.7%	34 36.6%	74 39.2%
>50 years	56 58.3%	59 63.4%	115 60.8%
Sex: Female, Male (Count of Participants)
Female	80 83.3%	75 80.6%	155 82%
Male	16 16.7%	18 19.4%	34 18%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2.1%	0 0%	2 1.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 2.1%	5 5.4%	7 3.7%
White	91 94.8%	87 93.5%	178 94.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1%	1 1.1%	2 1.1%
Region of Enrollment (participants) [Number]
United States	96 100%	93 100%	189 100%
Type of cancer (participants) [Number]
Breast	58 60.4%	57 61.3%	115 60.8%
Lung	1 1%	4 4.3%	5 2.6%
Other Cancer	37 38.5%	32 34.4%	69 36.5%
Planned number of chemotherapy cycles (participants) [Number]
<=4	48 50%	49 52.7%	97 51.3%
>4	48 50%	44 47.3%	92 48.7%
Type of chemotherapy (participants) [Number]
Taxane	57 59.4%	52 55.9%	109 57.7%
Cisplatin	4 4.2%	4 4.3%	8 4.2%
Carboplatin	1 1%	1 1.1%	2 1.1%
Oxaliplatin	24 25%	26 28%	50 26.5%
Combination	10 10.4%	10 10.8%	20 10.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Chemotherapy-induced Sensory Peripheral Neuropathy ≥ Grade 2
Description	The chemotherapy-induced sensory peripheral neuropathy utilized the sensory neuropathy item from the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grading: Grade 0=none; grade 1=loss of deep tendon reflexes or paresthesia, including tingling, but not interfering with function; grade 2=objective sensory alteration or paresthesia, including tingling, interfering with function, but not with activities of daily living; grade 3=sensory alteration or paresthesia interfering with activities of daily living; grade 4=permanent sensory losses that are disabling; and grade 5=death.
Time Frame	6 months post completion of chemotherapy treatment

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of assigned therapy.

Arm/Group Title	Vitamin E	Placebo
Arm/Group Description	Patients receive oral vitamin E twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.	Patients receive oral placebo twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.
Measure Participants	96	93
Number [percentage of participants]	34 35.4%	29 31.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin E, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Percentage of Patients Requiring Dose Reductions of Chemotherapy Due to Sensory Peripheral Neuropathy
Time Frame	6 months post completion of chemotherapy treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin E	Placebo
Arm/Group Description	Patients receive oral vitamin E twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.	Patients receive oral placebo twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.
Measure Participants	96	93
Number [percentage of patients]	3	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin E, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Percentage of Patients Stopping Chemotherapy Before Treatment is Complete Due to Sensory Peripheral Neuropathy
Time Frame	6 months post completion of chemotherapy treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin E	Placebo
Arm/Group Description	Patients receive oral vitamin E twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.	Patients receive oral placebo twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.
Measure Participants	96	93
Number [percentage of participants]	4 4.2%	3 3.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin E, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Time to Onset of Sensory Peripheral Neuropathy ≥ Grade 2
Description	Time to onset of sensory peripheral neuropathy was calculated using incidences of the adverse event while the patient was receiving chemotherapy.
Time Frame	6 months post completion of chemotherapy treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin E	Placebo
Arm/Group Description	Patients receive oral vitamin E twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.	Patients receive oral placebo twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.
Measure Participants	96	93
Median (95% Confidence Interval) [days]	58	69

5. Secondary Outcome

Title	Duration of Sensory Peripheral Neuropathy ≥ Grade 2
Description	Duration of sensory peripheral neuropathy is the time from onset of grade 2+ neuropathy until the neuropathy is resolved to grade 1 or less during chemotherapy treatment.
Time Frame	6 months post completion of chemotherapy treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin E	Placebo
Arm/Group Description	Patients receive oral vitamin E twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.	Patients receive oral placebo twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.
Measure Participants	33	27
Median (95% Confidence Interval) [days]	36	NA

Adverse Events

Time Frame	Prior to each cycle of chemotherapy to six months post chemotherapy completion
Arm/Group Title	Vitamin E		Placebo
Arm/Group Description	Patients receive oral vitamin E twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.		Patients receive oral placebo twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy.
All Cause Mortality
	Vitamin E		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vitamin E		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/96 (0%)		0/93 (0%)
Other (Not Including Serious) Adverse Events
	Vitamin E		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/96 (27.1%)		25/93 (26.9%)
Blood and lymphatic system disorders
Febrile neutropenia	0/96 (0%)	0	2/93 (2.2%)	2
Hemoglobin decreased	1/96 (1%)	1	1/93 (1.1%)	1
Cardiac disorders
Atrial fibrillation	0/96 (0%)	0	1/93 (1.1%)	1
Ear and labyrinth disorders
Tinnitus	1/96 (1%)	1	0/93 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/96 (2.1%)	2	2/93 (2.2%)	2
Constipation	0/96 (0%)	0	3/93 (3.2%)	4
Diarrhea	6/96 (6.3%)	9	3/93 (3.2%)	3
Esophageal mucositis	0/96 (0%)	0	1/93 (1.1%)	1
Flatulence	1/96 (1%)	1	0/93 (0%)	0
Nausea	5/96 (5.2%)	6	1/93 (1.1%)	1
Vomiting	5/96 (5.2%)	5	0/93 (0%)	0
General disorders
Edema limbs	0/96 (0%)	0	2/93 (2.2%)	2
Fatigue	2/96 (2.1%)	3	2/93 (2.2%)	2
General symptom	1/96 (1%)	1	0/93 (0%)	0
Immune system disorders
Hypersensitivity	1/96 (1%)	1	1/93 (1.1%)	1
Infections and infestations
Abdominal infection	0/96 (0%)	0	1/93 (1.1%)	1
Pharyngitis	1/96 (1%)	1	0/93 (0%)	0
Pneumonia	0/96 (0%)	0	1/93 (1.1%)	1
Skin infection	0/96 (0%)	0	1/93 (1.1%)	1
Upper respiratory infection	1/96 (1%)	1	0/93 (0%)	0
Urinary tract infection	1/96 (1%)	1	0/93 (0%)	0
Injury, poisoning and procedural complications
Vascular access complication	0/96 (0%)	0	1/93 (1.1%)	1
Investigations
Coagulopathy	0/96 (0%)	0	1/93 (1.1%)	2
Leukocyte count decreased	3/96 (3.1%)	6	2/93 (2.2%)	2
Lymphocyte count decreased	1/96 (1%)	2	0/93 (0%)	0
Neutrophil count decreased	2/96 (2.1%)	3	4/93 (4.3%)	6
Platelet count decreased	2/96 (2.1%)	2	2/93 (2.2%)	2
Metabolism and nutrition disorders
Anorexia	0/96 (0%)	0	1/93 (1.1%)	1
Dehydration	1/96 (1%)	1	0/93 (0%)	0
Hyperkalemia	0/96 (0%)	0	1/93 (1.1%)	1
Hypoalbuminemia	0/96 (0%)	0	1/93 (1.1%)	1
Hypocalcemia	0/96 (0%)	0	1/93 (1.1%)	1
Hypokalemia	0/96 (0%)	0	1/93 (1.1%)	1
Musculoskeletal and connective tissue disorders
Joint pain	2/96 (2.1%)	6	1/93 (1.1%)	1
Myalgia	2/96 (2.1%)	5	2/93 (2.2%)	2
Nervous system disorders
Dizziness	1/96 (1%)	1	0/93 (0%)	0
Headache	1/96 (1%)	1	0/93 (0%)	0
Intracranial hemorrhage	0/96 (0%)	0	1/93 (1.1%)	1
Ischemia cerebrovascular	1/96 (1%)	1	0/93 (0%)	0
Peripheral sensory neuropathy	3/96 (3.1%)	3	4/93 (4.3%)	7
Syncope	1/96 (1%)	1	0/93 (0%)	0
Psychiatric disorders
Anxiety	0/96 (0%)	0	1/93 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/96 (0%)	0	3/93 (3.2%)	3
Hemorrhage nasal	0/96 (0%)	0	1/93 (1.1%)	1
Hypoxia	1/96 (1%)	1	0/93 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	2/96 (2.1%)	3	0/93 (0%)	0
Hand-and-foot syndrome	1/96 (1%)	1	0/93 (0%)	0
Pruritus	1/96 (1%)	3	0/93 (0%)	0
Rash desquamating	1/96 (1%)	1	1/93 (1.1%)	1
Vascular disorders
Hemorrhage	0/96 (0%)	0	1/93 (1.1%)	1
Hot flashes	0/96 (0%)	0	1/93 (1.1%)	1
Hypertension	0/96 (0%)	0	1/93 (1.1%)	1
Thrombosis	0/96 (0%)	0	5/93 (5.4%)	5
Visceral arterial ischemia	0/96 (0%)	0	1/93 (1.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.