Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00302159
• Collaborator: (none)
• Enrollment: 43
• Locations: 3
• Arm: 1
• Duration (Months): 104
• Patients Per Site: 14.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Background:

• Radiation therapy with temozolomide (an anti-cancer drug) is standard therapy for treating brain tumors called glioblastomas.

• The drug valproic acid, currently approved for treating seizures, has been shown in laboratory tests to increase the radiosensitivity of glioma cells.

Objectives:

-To determine the effectiveness of adding valproic acid to standard treatment with radiation therapy and temozolomide for treating glioblastoma.

Eligibility:

-Patients 18 years of age and older with glioblastoma multiforme who have not been previously treated with chemotherapy of radiation.

Design:

• This Phase II trial will enroll 41 patients.

• Patients will receive radiation therapy to the brain once a day, Monday through Friday, for 6 1/2 weeks.

• Patients will take temozolomide once a day by mouth, Monday through Friday, during the period of radiation treatment. Starting 4 weeks after radiation therapy, patients will take temozolomide once a day for 5 days every 28 days for a total of six cycles.

• Patients will receive valproic acid by mouth twice a day beginning 1 week prior to the first day of radiation therapy and continuing until the completion of chemotherapy and radiation therapy.

• Patients will have follow-up visits 1 month after completing therapy, then every 3 months for 2 years, and then every 6 months for 3 years. Follow-up includes a physical examination, blood tests and magnetic resonance imaging of the brain.

Condition or Disease	Intervention/Treatment	Phase
High Grade Gliomas; Brain Tumors	Procedure: adjuvant therapy; Drug: Temozolomide; Drug: Valproic Acid; Radiation: Radiation therapy	Phase 2

Detailed Description

BACKGROUND:

• Histone deacetylase inhibitors (HDACi) have recently been shown to enhance the radiosensitivity of glioma cells both in vitro and in vivo.

• Valproic acid has also recently been demonstrated to be a potent HDAC.

• Valproic acid has a long clinical history in patients with and without brain tumors and is known to cross the blood-brain barrier. However, the use of valproic acid in combination with temozolomide and radiotherapy for patients with high-grade gliomas has never been tested.

OBJECTIVES:

-The primary measure of efficacy will be progression free survival and overall survival.

ELIGIBILITY:

• Patients greater than 18 years old

• Diagnosis glioblastoma multiforme

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

• Patients who have not been previously treated with chemotherapy or radiation

DESIGN:

• This is a Phase II trial to determine the efficacy of valproic acid in combination with external beam radiation therapy and temozolomide in patients with high-grade gliomas.

• Patients will be treated with external beam radiation therapy in a standard manner with temozolomide given daily during the radiation. The valproic acid will be administered daily beginning one week prior to the first day of irradiation and continuing until the completion of chemoradiation.

• We anticipate that accrual to this trial of 41 patients will take approximately 1 year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of the Histone Deacetylase Inhibitor Valproic Acid in Combination With Temodar and Radiation Therapy in Patients With High Grade Gliomas: Multi-Institutional Trial
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Valproic Acid Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.	Procedure: adjuvant therapy; Drug: Temozolomide; Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation.; Other Names: Temodar ; Drug: Valproic Acid; Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.; Other Names: Depakote ; Radiation: Radiation therapy; External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.

Outcome Measures

Primary Outcome Measures

1. Median Progression Free Survival. [up to 51 months]

   Progression free survival is the interval from initiation of treatment on protocol to symptomatic or radiographic progression. Progressive disease is a >25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.

2. Percentage of Participants With Progression Free Survival at 6, 12, and 24 Months [6, 12, and 24 months]

   Percentage of participants who were progression free by 6, 12, or 24 months. Progressive disease is a >25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.

3. Number of Participants With Best Response [up to 63.8 months]

   Best response recorded from the start of treatment until disease progression/recurrence. Complete response is complete resolution of all contrast enhancing tumor documented at initiation of treatment on protocol, with no appearance of new lesions. Partial response is a >50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Minor response is a >25%, but <50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Stable disease is a change in tumor size less than MR but not demonstrating progressive disease. Progressive disease is a >25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol. Not evaluable means the participant cannot be evaluated (e.g., quality of scan).

4. Median Overall Survival [up to 63.8 months]

   Survival is the interval from the initiation of treatment on protocol to date of death.

5. Percentage of Participants With Overall Survival at 6, 12, and 24 Months [6, 12, and 24 months]

   Percentage of participants who were alive at 6, 12, and 24 months.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [6 years, 7 months and 27 days]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

Histological diagnosis:

Pathologically confirmed glioblastoma multiforme.

Histologic diagnosis of glioblastoma multiforme (GBM) will have been established by biopsy or resection no more than 6 weeks prior to enrollment.

The patient is a candidate for definitive external beam radiotherapy.

Patients must be older than 18 years with a life expectancy greater than 8 weeks.

Patients should have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Patients must have a primary medical oncologist in the community who is willing to collaborate with the Radiation Oncology Branch (ROB) staff in the clinical management of the patient, specifically in the prescription of Temozolomide and toxicity monitoring in the adjuvant phase.

Laboratory functions:

Adequate bone marrow function defined as a peripheral absolute granulocyte count of greater than 1500/mm^{3, hemoglobin greater than 10gm/dL, and platelet count greater than 100,000/mm}3.

Adequate liver function, defined as bilirubin and serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) less than 2 x the upper limit of normal.

Serum creatinine less than 1.5 mg/dl.

Serum albumin greater than 0.75 x normal.

All patients or their legal guardian must sign a document of informed consent indicating their understanding of the investigational nature and the risks of this study BEFORE any of the protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility).

Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.

EXCLUSION CRITERIA

Prior therapy:

Patients who have previously received valproic acid.

Patients who have previously received radiation therapy to the brain.

Patients who have received chemotherapy for the treatment of their high grade glioma or who are currently receiving other investigational chemotherapeutic agents.

Patients with a known history of disorders of urea metabolism.

Concurrent therapy:

The concurrent use of sulfamethoxazole, salicylates or naproxen is not allowed.

Patients with a history of or concurrent second malignancy other than non-melanoma skin cancer or cervical cancer less than 3 years since GBM diagnosis.

Pregnant or breast-feeding females are excluded because of the potential mutagenic effects on a developing fetus or newborn.

Clinically significant unrelated systemic illness which in the judgement of the Principal or Associate Investigator would compromise the patient's ability to tolerate this therapy or are likely to interfere with the study procedures or results, including but not limited to Insulin dependent diabetes.

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
2	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-6056
3	Virginia Commonwealth University	Richmond	Virginia	United States	23284

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Kevin A Camphausen, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Davis FG, McCarthy BJ, Freels S, Kupelian V, Bondy ML. The conditional probability of survival of patients with primary malignant brain tumors: surveillance, epidemiology, and end results (SEER) data. Cancer. 1999 Jan 15;85(2):485-91.
• Loeffler JS, Alexander E 3rd, Shea WM, Wen PY, Fine HA, Kooy HM, Black PM. Radiosurgery as part of the initial management of patients with malignant gliomas. J Clin Oncol. 1992 Sep;10(9):1379-85.

• Responsible Party: Kevin Camphausen, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00302159
• Other Study ID Numbers: 060112; 06-C-0112; NCT00313664
• First Posted: Mar 13, 2006
• Last Update Posted: Aug 18, 2016
• Last Verified: Jul 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Kevin Camphausen, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC): Chemotherapy; Radiation; Brain Tumor; GBM; Radiosensitizer; Glioblastoma; Glioblastoma Multiforme
• Additional relevant MeSH terms: Glioma; Brain Neoplasms; Temozolomide; Valproic Acid

Study Results

Participant Flow

Arm/Group Title	Valproic Acid
Arm/Group Description	adjuvant therapy Temozolomide Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation. Valproic Acid Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Radiation therapy External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
Period Title: Overall Study
STARTED	43
COMPLETED	41
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Valproic Acid
Arm/Group Description	adjuvant therapy Temozolomide Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation. Valproic Acid Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Radiation therapy External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
Overall Participants	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.88 (11.33)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	39 90.7%
>=65 years	4 9.3%
Sex: Female, Male (Count of Participants)
Female	14 32.6%
Male	29 67.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 11.6%
White	35 81.4%
More than one race	0 0%
Unknown or Not Reported	2 4.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4.7%
Not Hispanic or Latino	41 95.3%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	43 100%

Outcome Measures

1. Primary Outcome

Title	Median Progression Free Survival.
Description	Progression free survival is the interval from initiation of treatment on protocol to symptomatic or radiographic progression. Progressive disease is a >25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.
Time Frame	up to 51 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valproic Acid
Arm/Group Description	adjuvant therapy Temozolomide Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation. Valproic Acid Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Radiation therapy External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
Measure Participants	43
Median (95% Confidence Interval) [months]	10.5

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame	6 years, 7 months and 27 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valproic Acid
Arm/Group Description	adjuvant therapy Temozolomide Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation. Valproic Acid Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Radiation therapy External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
Measure Participants	43
Number [participants]	43 100%

3. Primary Outcome

Title	Percentage of Participants With Progression Free Survival at 6, 12, and 24 Months
Description	Percentage of participants who were progression free by 6, 12, or 24 months. Progressive disease is a >25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.
Time Frame	6, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valproic Acid
Arm/Group Description	Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. adjuvant therapy Temozolomide: Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation. Valproic Acid: Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Radiation therapy: External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
Measure Participants	43
6 months	70 162.8%
12 months	43 100%
24 months	38 88.4%

4. Primary Outcome

Title	Number of Participants With Best Response
Description	Best response recorded from the start of treatment until disease progression/recurrence. Complete response is complete resolution of all contrast enhancing tumor documented at initiation of treatment on protocol, with no appearance of new lesions. Partial response is a >50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Minor response is a >25%, but <50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Stable disease is a change in tumor size less than MR but not demonstrating progressive disease. Progressive disease is a >25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol. Not evaluable means the participant cannot be evaluated (e.g., quality of scan).
Time Frame	up to 63.8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valproic Acid
Arm/Group Description	Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. adjuvant therapy Temozolomide: Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation. Valproic Acid: Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Radiation therapy: External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
Measure Participants	43
Complete Response	0 0%
Partial Response	0 0%
Minor Response	0 0%
Stable Disease	27 62.8%
Progressive Disease	7 16.3%
Not Evaluable	9 20.9%

5. Primary Outcome

Title	Median Overall Survival
Description	Survival is the interval from the initiation of treatment on protocol to date of death.
Time Frame	up to 63.8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valproic Acid
Arm/Group Description	Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. adjuvant therapy Temozolomide: Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation. Valproic Acid: Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Radiation therapy: External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
Measure Participants	43
Median (95% Confidence Interval) [months]	29.6

6. Primary Outcome

Title	Percentage of Participants With Overall Survival at 6, 12, and 24 Months
Description	Percentage of participants who were alive at 6, 12, and 24 months.
Time Frame	6, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valproic Acid
Arm/Group Description	Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. adjuvant therapy Temozolomide: Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation. Valproic Acid: Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Radiation therapy: External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
Measure Participants	43
6 months	97 225.6%
12 months	86 200%
24 months	56 130.2%

Adverse Events

Arm/Group Title	Valproic Acid
Arm/Group Description	adjuvant therapy Temozolomide Orally 75mg/m^2 first day of radiation until completion. Restart 4 weeks post radiation. Valproic Acid Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide. Radiation therapy External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.
All Cause Mortality
	Valproic Acid
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Valproic Acid
	Affected / at Risk (%)	# Events
Total	17/43 (39.5%)
Blood and lymphatic system disorders
Lymphopenia	1/43 (2.3%)	1
Platelets	2/43 (4.7%)	3
Eye disorders
Vision-blurred vision	1/43 (2.3%)	1
Gastrointestinal disorders
Dehydration	1/43 (2.3%)	1
General disorders
Death not associated with CTCAE term::Disease progression NOS	1/43 (2.3%)	1
Fatigue (asthenia, lethargy, malaise)	1/43 (2.3%)	1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	1/43 (2.3%)	1
Infections and infestations
Infection - Other (Specify, pneumonia)	1/43 (2.3%)	1
Metabolism and nutrition disorders
Amylase	1/43 (2.3%)	1
Metabolic/Laboratory - Other (Specify, high ammonia)	1/43 (2.3%)	1
Nervous system disorders
Ataxia (incoordination)	3/43 (7%)	3
Confusion	2/43 (4.7%)	2
Encephalopathy	1/43 (2.3%)	1
Hemorrhage, CNS	2/43 (4.7%)	2
Mood alteration::Agitation	2/43 (4.7%)	2
Neuropathy: motor	3/43 (7%)	3
Pain::Head/headache	1/43 (2.3%)	1
Seizure	4/43 (9.3%)	4
Speech impairment (e.g., dysphasia or aphasia)	2/43 (4.7%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/43 (2.3%)	1
Hypoxia	1/43 (2.3%)	2
Pulmonary/Upper Respiratory - Other (Specify, PE)	1/43 (2.3%)	1
Other (Not Including Serious) Adverse Events
	Valproic Acid
	Affected / at Risk (%)	# Events
Total	39/43 (90.7%)
Blood and lymphatic system disorders
Edema: head and neck	4/43 (9.3%)	4
Edema: limb	4/43 (9.3%)	5
Hemoglobin	13/43 (30.2%)	23
INR (International Normalized Ratio of prothrombin time)	1/43 (2.3%)	1
Leukocytes (total WBC)	14/43 (32.6%)	42
Lymphatics - Other (Specify)	2/43 (4.7%)	3
Lymphopenia	27/43 (62.8%)	79
Neutrophils/granulocytes (ANC/AGC)	8/43 (18.6%)	16
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	1/43 (2.3%)	1
Platelets	27/43 (62.8%)	63
Cardiac disorders
Cardiac General - Other (Specify, systolic ejection murmur noted)	1/43 (2.3%)	1
Supraventricular and nodal arrhythmia::Sinus tachycardia	1/43 (2.3%)	1
Ear and labyrinth disorders
Auditory/Ear - Other (Specify, decreased hearing)	1/43 (2.3%)	1
Hearing: patients without baseline audiogram and not enrolled in a monitoring program	2/43 (4.7%)	2
Otitis, middle ear (non-infectious)	1/43 (2.3%)	2
Pain::External ear	1/43 (2.3%)	1
Tinnitus	4/43 (9.3%)	4
Endocrine disorders
Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae)	2/43 (4.7%)	2
Eye disorders
Eyelid dysfunction	1/43 (2.3%)	2
Nystagmus	2/43 (4.7%)	2
Ocular/Visual - Other (Specify)	3/43 (7%)	3
Vision-blurred vision	4/43 (9.3%)	4
Vision-flashing lights/floaters	1/43 (2.3%)	1
Vision-photophobia	1/43 (2.3%)	1
Watery eye (epiphora, tearing)	2/43 (4.7%)	2
Gastrointestinal disorders
Anorexia	6/43 (14%)	7
Constipation	17/43 (39.5%)	19
Dehydration	2/43 (4.7%)	2
Diarrhea	2/43 (4.7%)	3
Dry mouth/salivary gland (xerostomia)	1/43 (2.3%)	1
Dysphagia (difficulty swallowing)	2/43 (4.7%)	2
Flatulence	2/43 (4.7%)	2
Gastritis (including bile reflux gastritis)	1/43 (2.3%)	1
Gastrointestinal - Other (Specify, GERD)	1/43 (2.3%)	1
Heartburn/dyspepsia	1/43 (2.3%)	1
Hemorrhage, GI::Anus	1/43 (2.3%)	1
Hemorrhoids	1/43 (2.3%)	1
Mucositis/stomatitis (clinical exam)::Oral cavity	2/43 (4.7%)	2
Mucositis/stomatitis (functional/symptomatic)::Oral cavity	1/43 (2.3%)	1
Nausea	23/43 (53.5%)	30
Pain::Abdomen NOS	3/43 (7%)	4
Pain::Dental/teeth/peridontal	1/43 (2.3%)	1
Pain::Esophagus	1/43 (2.3%)	1
Taste alteration (dysgeusia)	3/43 (7%)	3
Vomiting	8/43 (18.6%)	8
General disorders
Fatigue (asthenia, lethargy, malaise)	25/43 (58.1%)	34
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	2/43 (4.7%)	2
Insomnia	7/43 (16.3%)	7
Pain - Other (Specify,jaw; right shoulder; whole body)	2/43 (4.7%)	3
Pain::Pain NOS	1/43 (2.3%)	2
Sweating (diaphoresis)	1/43 (2.3%)	1
Weight gain	1/43 (2.3%)	1
Weight loss	2/43 (4.7%)	2
Hepatobiliary disorders
Pancreatitis	2/43 (4.7%)	2
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	4/43 (9.3%)	4
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Conjunctiva	1/43 (2.3%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Middle ear (otitis media)	1/43 (2.3%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis)	2/43 (4.7%)	2
Infection with unknown ANC::Bronchus	1/43 (2.3%)	1
Infection with unknown ANC::Paranasal	1/43 (2.3%)	1
Infection with unknown ANC::Skin (cellulites)	1/43 (2.3%)	1
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)	15/43 (34.9%)	19
AST, SGOT(serum glutamic oxaloacetic transaminase)	6/43 (14%)	7
Albumin, serum-low (hypoalbuminemia)	27/43 (62.8%)	41
Alkaline phosphatase	2/43 (4.7%)	2
Amylase	6/43 (14%)	9
Bilirubin (hyperbilirubinemia)	7/43 (16.3%)	10
Calcium, serum-high (hypercalcemia)	5/43 (11.6%)	5
Calcium, serum-low (hypocalcemia)	4/43 (9.3%)	6
Creatinine	5/43 (11.6%)	6
Glucose, serum-high (hyperglycemia)	4/43 (9.3%)	8
Lipase	6/43 (14%)	10
Magnesium, serum-high (hypermagnesemia)	15/43 (34.9%)	18
Magnesium, serum-low (hypomagnesemia)	3/43 (7%)	3
Metabolic/Laboratory - Other (Specify)	4/43 (9.3%)	6
Phosphate, serum-low (hypophosphatemia)	2/43 (4.7%)	3
Potassium, serum-high (hyperkalemia)	14/43 (32.6%)	26
Sodium, serum-high (hypernatremia)	11/43 (25.6%)	16
Sodium, serum-low (hyponatremia)	11/43 (25.6%)	20
Uric acid, serum-high (hyperuricemia)	6/43 (14%)	9
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/43 (2.3%)	1
Extremity-upper (function)	1/43 (2.3%)	1
Muscle weakness, generalized or specific area (not due to neuropathy)::Extremity-upper	2/43 (4.7%)	3
Muscle weakness, generalized or specific area (not due to neuropathy)::Facial	1/43 (2.3%)	1
Muscle weakness, generalized or specific area (not due to neuropathy)::Left-sided	1/43 (2.3%)	1
Muscle weakness, generalized or specific area (not due to neuropathy)::Right-sided	2/43 (4.7%)	2
Musculoskeletal/Soft Tissue - Other (Specify, ® rotator cuff injury)	1/43 (2.3%)	1
Pain::Back	2/43 (4.7%)	2
Pain::Extremity-limb	2/43 (4.7%)	3
Pain::Joint	4/43 (9.3%)	4
Pain::Muscle	2/43 (4.7%)	3
Nervous system disorders
Ataxia (incoordination)	10/43 (23.3%)	15
Cognitive disturbance	1/43 (2.3%)	1
Confusion	16/43 (37.2%)	19
Dizziness	5/43 (11.6%)	7
Encephalopathy	2/43 (4.7%)	2
Extrapyramidal/involuntary movement/restlessness	2/43 (4.7%)	3
Memory impairment	8/43 (18.6%)	8
Mental status	1/43 (2.3%)	1
Mood alteration::Agitation	6/43 (14%)	7
Mood alteration::Anxiety	5/43 (11.6%)	7
Mood alteration::Depression	4/43 (9.3%)	4
Mood alteration::Euphoria	1/43 (2.3%)	2
Neurology - Other (Specify)	5/43 (11.6%)	5
Neuropathy: cranial::CN II Vision	1/43 (2.3%)	1
Neuropathy: cranial::CN V Motor-jaw muscles; Sensory-facial	2/43 (4.7%)	2
Neuropathy: cranial::CN VII Motor-face; Sensory-taste	1/43 (2.3%)	1
Neuropathy: cranial::CN VIII Hearing and balance	1/43 (2.3%)	2
Neuropathy: motor	11/43 (25.6%)	12
Neuropathy: sensory	6/43 (14%)	10
Pain::Head/headache	14/43 (32.6%)	20
Psychosis (hallucinations/delusions)	2/43 (4.7%)	2
Pyramidal tract dysfunction	1/43 (2.3%)	1
Seizure	11/43 (25.6%)	18
Somnolence/depressed level of consciousness	6/43 (14%)	6
Speech impairment (e.g., dysphasia or aphasia)	4/43 (9.3%)	5
Tremor	4/43 (9.3%)	6
Renal and urinary disorders
Incontinence, urinary	2/43 (4.7%)	2
Reproductive system and breast disorders
Hemorrhage, GU::Vagina	1/43 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Bronchospasm, wheezing	1/43 (2.3%)	1
Cough	4/43 (9.3%)	4
Pain::Chest/thorax NOS	1/43 (2.3%)	1
Pain::Throat/pharynx/larynx	2/43 (4.7%)	2
Pulmonary/Upper Respiratory - Other (Specify, pulomonary embolism)	1/43 (2.3%)	1
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify, cyst R axilla)	1/43 (2.3%)	1
Dry skin	1/43 (2.3%)	1
Hair loss/alopecia (scalp or body)	23/43 (53.5%)	23
Hyperpigmentation	2/43 (4.7%)	2
Hypopigmentation	1/43 (2.3%)	1
Pain::Scalp	2/43 (4.7%)	2
Pruritus/itching	2/43 (4.7%)	2
Rash/desquamation	4/43 (9.3%)	5
Rash: acne/acneiform	2/43 (4.7%)	3
Rash: dermatitis associated with radiation::Chemoradiation	4/43 (9.3%)	4
Rash: dermatitis associated with radiation::Radiation	5/43 (11.6%)	6
Vascular disorders
Hypertension	2/43 (4.7%)	2
Hypotension	1/43 (2.3%)	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.