Carboplatin, Vincristine, and Temozolomide in Treating Children With Progressive and/or Symptomatic Low-Grade Glioma

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00077207
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 66
• Location: 1
• Arm: 1
• Duration (Months): 113
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin, vincristine, and temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells.

PURPOSE: This pilot study is studying giving carboplatin and vincristine together with temozolomide in treating children with progressive and/or symptomatic low-grade glioma.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumor; Central Nervous System Tumor	Drug: carboplatin; Drug: temozolomide; Drug: vincristine sulfate	N/A

Detailed Description

OBJECTIVES:

Primary

• Determine the feasibility and toxicity of an induction and maintenance regimen comprising carboplatin, vincristine, and temozolomide in children with progressive and/or symptomatic low-grade gliomas.

Secondary

• Determine response rate in patients treated with this regimen.

• Determine 3-year progression-free survival and overall survival of patients treated with this regimen.

• Correlate response and progression-free survival with the genomic profile of tumors in patients treated with this regimen.

OUTLINE: This is a pilot study.

• Induction therapy: Patients receive carboplatin IV over 1 hour on days 1, 8, 15, and 22; vincristine IV on days 1, 8, 15, 22, 29, and 36; and oral temozolomide on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy.

• Maintenance therapy: Patients receive carboplatin and temozolomide as in induction therapy and vincristine IV on days 1, 8, and 15. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study within 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study Using Carboplatin, Vincristine And Temozolomide For Children ≤ 10 Years With Progressive/Symptomatic Low-Grade Gliomas
• Study Start Date: Jul 1, 2004
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (carboplatin, vincristine sulfate, temozolomide) Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression.

Drug: carboplatin; Given IV; Other Names: Paraplatin NSC #241240 ; Drug: temozolomide; Given orally; Other Names: Temodar NSC# 362856 ; Drug: vincristine sulfate; Given IV; Other Names: Oncovin VCR LCR NSC #67574

Outcome Measures

Primary Outcome Measures

1. Short Term Feasibility Success [24 weeks]

   Success is defined as the completion of induction plus one cycle of maintenance within 24 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage. Failure to complete the induction and one cycle of maintenance within 24 weeks counts as a short-term-feasibility failure.

2. Long Term Feasibility Success [60 weeks]

   Success is defined as the completion of induction plus four cycles of maintenance within 60 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage. If the participant completes all therapy within 60 weeks the patient is a long-term feasibility success. As such, a patient who experiences short term feasibility failure can be classified as a long-term feasibility success.

Secondary Outcome Measures

1. Number of Participants Who Experienced Toxic Death [Up to 6 years after the start of protocol therapy]

   Primary safety endpoints are (1) the occurrence of toxic death, which is death during treatment that is not primarily attributable to disease progression, and (2) the occurrence of grade 4 allergy to carboplatin.

2. Number of Participants Who Experienced a Grade 3 or 4 Thrombocytopenia and/or Neutropenia. [Up to 18 months of protocol therapy]

   Occurence of grade 3 or 4 thrombocytopenia or neutropenia while receiving protocol therapy.

3. Percent Probability of Progression-free Survival (PFS) [3 years]

   Percentage probability of being alive and without the occurrence of disease progression 3 years following enrollment.

4. Percentage Probability of Event-free Survival (EFS) [Six years]

   Percentage probability of being alive and without the occurrence of disease progression or second malignant neoplasm 6 years following enrollment.

5. Total Number of Patients Experiencing a Response [Up to 18 months of protocol therapy]

   Response as complete response, partial response, stable disease, or progressive disease using three-dimensional imaging measurements (preferable) or two-dimensional imaging measurements, as well as the response in the context of multiple lesions or disseminated disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 10 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed progressive and/or symptomatic low-grade glioma, including any of the following:

• WHO grade I or II astrocytoma

• Grade I or II oligodendrogliomas

• Mixed oligodendrogliomas

• Gangliogliomas

• Measurable disease

• Progressive and/or symptomatic supratentorial or spinal cord tumors that cannot be removed for anatomical reasons are allowed

• Optic pathway tumors allowed provided there is evidence of progressive disease by MRI and/or symptoms of deteriorating vision, progressive hypothalamic/pituitary dysfunction, or diencephalic syndrome

• Dorsally exophytic brainstem gliomas that were previously resected more than 50% are allowed provided the residual tumor shows progression (with or without symptoms)

• No diffuse brain stem tumors

• No type 1 neurofibromatosis

PATIENT CHARACTERISTICS:

Age

• 10 and under

Performance status

• ECOG 0-2

• Lansky 50-100%

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin ≥ 8.0 gm/dL

• Absolute neutrophil count ≥ 1,000/mm^3

• Platelet count ≥ 100,000/mm^3

Hepatic

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

• ALT < 2.5 times ULN

Renal

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR

• Creatinine ≤ 0.8 mg/dL (age 5 and under) OR ≤ 1.0 mg/dL (age 6 to10)

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunomodulating agents

Chemotherapy

• No other concurrent anticancer chemotherapy

Endocrine therapy

• Prior corticosteroids allowed

• No concurrent corticosteroids except for the treatment of increased intracranial pressure

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics

• Prior surgery allowed

Other

• No other prior therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Oncology Group	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Murali M. Chintagumpala, MD, Texas Children's Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00077207
• Other Study ID Numbers: ACNS0223; CDR0000350005; COG-ACNS0223; NCI-2012-02572
• First Posted: Feb 11, 2004
• Last Update Posted: May 16, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Children's Oncology Group: untreated childhood cerebellar astrocytoma; untreated childhood visual pathway and hypothalamic glioma; childhood spinal cord neoplasm; childhood oligodendroglioma; childhood low-grade cerebral astrocytoma
• Additional relevant MeSH terms: Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Carboplatin; Vincristine; Temozolomide

Study Results

Participant Flow

Arm/Group Title	Treatment (Carboplatin, Vincristine Sulfate, Temozolomide)
Arm/Group Description	Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. carboplatin: Given IV temozolomide: Given orally vincristine sulfate: Given IV
Period Title: Overall Study
STARTED	66
COMPLETED	36
NOT COMPLETED	30

Baseline Characteristics

Arm/Group Title	Treatment (Carboplatin, Vincristine Sulfate, Temozolomide)
Arm/Group Description	Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. carboplatin: Given IV temozolomide: Given orally vincristine sulfate: Given IV
Overall Participants	66
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	4
Sex: Female, Male (Count of Participants)
Female	29 43.9%
Male	37 56.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 1.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 9.1%
White	49 74.2%
More than one race	0 0%
Unknown or Not Reported	10 15.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 16.7%
Not Hispanic or Latino	52 78.8%
Unknown or Not Reported	3 4.5%
Region of Enrollment (participants) [Number]
United States	61 92.4%
Canada	1 1.5%
Australia	4 6.1%

Outcome Measures

1. Primary Outcome

Title	Short Term Feasibility Success
Description	Success is defined as the completion of induction plus one cycle of maintenance within 24 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage. Failure to complete the induction and one cycle of maintenance within 24 weeks counts as a short-term-feasibility failure.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Fourteen (14) patients were considered not evaluable for short-term toxicity because: ineligible - 1 patient; progression during induction - 9 patients; progression during maintenance 2 patients; parent preference - 1 patient and infection resulting in termination of protocol therapy - 1 patient.

Arm/Group Title	Treatment (Carboplatin, Vincristine Sulfate, Temozolomide)
Arm/Group Description	Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. carboplatin: Given IV temozolomide: Given orally vincristine sulfate: Given IV
Measure Participants	52
Number [participants]	25 37.9%

2. Primary Outcome

Title	Long Term Feasibility Success
Description	Success is defined as the completion of induction plus four cycles of maintenance within 60 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage. If the participant completes all therapy within 60 weeks the patient is a long-term feasibility success. As such, a patient who experiences short term feasibility failure can be classified as a long-term feasibility success.
Time Frame	60 weeks

Outcome Measure Data

Analysis Population Description

Fourteen (14) patients were considered not evaluable for long-term toxicity because: ineligible - 1 patient; progression during induction - 9 patients; progression during maintenance 2 patients; parent preference - 1 patient and infection resulting in termination of protocol therapy - 1 patient.

Arm/Group Title	Treatment (Carboplatin, Vincristine Sulfate, Temozolomide)
Arm/Group Description	Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. carboplatin: Given IV temozolomide: Given orally vincristine sulfate: Given IV
Measure Participants	52
Number [participants]	41 62.1%

3. Secondary Outcome

Title	Number of Participants Who Experienced Toxic Death
Description	Primary safety endpoints are (1) the occurrence of toxic death, which is death during treatment that is not primarily attributable to disease progression, and (2) the occurrence of grade 4 allergy to carboplatin.
Time Frame	Up to 6 years after the start of protocol therapy

Outcome Measure Data

Analysis Population Description

Sixty-five (65) eligible patients were enrolled and received protocol therapy. These patients are considered for this outcome measure.

Arm/Group Title	Carboplatin, Vincristine Sulfate, Temozolomide)
Arm/Group Description	Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. carboplatin: Given IV temozolomide: Given orally vincristine sulfate: Given IV
Measure Participants	65
Count of Participants [Participants]	0 0%

4. Secondary Outcome

Title	Number of Participants Who Experienced a Grade 3 or 4 Thrombocytopenia and/or Neutropenia.
Description	Occurence of grade 3 or 4 thrombocytopenia or neutropenia while receiving protocol therapy.
Time Frame	Up to 18 months of protocol therapy

Outcome Measure Data

Analysis Population Description

Sixty-five (65) eligible patients were enrolled and received protocol therapy. These patients are considered for this outcome measure.

Arm/Group Title	Carboplatin, Vincristine Sulfate, Temozolomide)
Arm/Group Description	Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. carboplatin: Given IV temozolomide: Given orally vincristine sulfate: Given IV
Measure Participants	65
Count of Participants [Participants]	43 65.2%

5. Secondary Outcome

Title	Percent Probability of Progression-free Survival (PFS)
Description	Percentage probability of being alive and without the occurrence of disease progression 3 years following enrollment.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Sixty-five (65) eligible patients were enrolled and received protocol therapy. These patients are considered for this outcome measure.

Arm/Group Title	Carboplatin, Vincristine Sulfate, Temozolomide)
Arm/Group Description	Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. carboplatin: Given IV temozolomide: Given orally vincristine sulfate: Given IV
Measure Participants	65
Number (95% Confidence Interval) [Percent probability PFS]	60.59

6. Secondary Outcome

Title	Percentage Probability of Event-free Survival (EFS)
Description	Percentage probability of being alive and without the occurrence of disease progression or second malignant neoplasm 6 years following enrollment.
Time Frame	Six years

Outcome Measure Data

Analysis Population Description

Sixty-five (65) eligible patients were enrolled and received protocol therapy. These patients are considered for this outcome measure.

Arm/Group Title	Carboplatin, Vincristine Sulfate, Temozolomide)
Arm/Group Description	Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. carboplatin: Given IV temozolomide: Given orally vincristine sulfate: Given IV
Measure Participants	65
Number (95% Confidence Interval) [percent probability EFS]	40.89

7. Secondary Outcome

Title	Total Number of Patients Experiencing a Response
Description	Response as complete response, partial response, stable disease, or progressive disease using three-dimensional imaging measurements (preferable) or two-dimensional imaging measurements, as well as the response in the context of multiple lesions or disseminated disease.
Time Frame	Up to 18 months of protocol therapy

Outcome Measure Data

Analysis Population Description

Sixty-five (65) eligible patients were enrolled and received protocol therapy. Of these patients, 60 had data submission sufficient to determine response.

Arm/Group Title	Carboplatin, Vincristine Sulfate, Temozolomide)
Arm/Group Description	Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. carboplatin: Given IV temozolomide: Given orally vincristine sulfate: Given IV
Measure Participants	60
Complete response	2 3%
Partial response	15 22.7%
Stable disease	36 54.5%
Progressive disease	7 10.6%

Adverse Events

Adverse Event Reporting Description	66 patients enrolled, 64 reported for adverse events as 1 patient was ineligible and 1 patient missed a reporting period.
Arm/Group Title	Treatment (Carboplatin, Vincristine Sulfate, Temozolomide)
Arm/Group Description	Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. carboplatin: Given IV temozolomide: Given orally vincristine sulfate: Given IV
All Cause Mortality
	Treatment (Carboplatin, Vincristine Sulfate, Temozolomide)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Carboplatin, Vincristine Sulfate, Temozolomide)
	Affected / at Risk (%)	# Events
Total	6/64 (9.4%)
Eye disorders
Eye disorders - Other, specify	1/64 (1.6%)
Investigations
Alanine aminotransferase increased	1/64 (1.6%)
Neutrophil count decreased	1/64 (1.6%)
Platelet count decreased	1/64 (1.6%)
Renal and urinary disorders
Proteinuria	1/64 (1.6%)
Respiratory, thoracic and mediastinal disorders
Cough	1/64 (1.6%)
Other (Not Including Serious) Adverse Events
	Treatment (Carboplatin, Vincristine Sulfate, Temozolomide)
	Affected / at Risk (%)	# Events
Total	50/64 (78.1%)
Blood and lymphatic system disorders
Anemia	33/64 (51.6%)
Febrile neutropenia	10/64 (15.6%)
Cardiac disorders
Cardiac disorders - Other, specify	1/64 (1.6%)
Left ventricular systolic dysfunction	1/64 (1.6%)
Sinus tachycardia	1/64 (1.6%)
Ear and labyrinth disorders
Middle ear inflammation	2/64 (3.1%)
Endocrine disorders
Cushingoid	3/64 (4.7%)
Eye disorders
Blurred vision	3/64 (4.7%)
Extraocular muscle paresis	1/64 (1.6%)
Eye disorders - Other, specify	3/64 (4.7%)
Optic nerve disorder	1/64 (1.6%)
Photophobia	2/64 (3.1%)
Watering eyes	1/64 (1.6%)
Gastrointestinal disorders
Abdominal distension	1/64 (1.6%)
Abdominal pain	10/64 (15.6%)
Constipation	16/64 (25%)
Diarrhea	9/64 (14.1%)
Dysphagia	1/64 (1.6%)
Ileus	2/64 (3.1%)
Mucositis oral	3/64 (4.7%)
Nausea	16/64 (25%)
Oral pain	3/64 (4.7%)
Rectal hemorrhage	1/64 (1.6%)
Toothache	1/64 (1.6%)
Vomiting	23/64 (35.9%)
General disorders
Edema face	2/64 (3.1%)
Facial pain	1/64 (1.6%)
Fatigue	13/64 (20.3%)
Fever	18/64 (28.1%)
Flu like symptoms	1/64 (1.6%)
General disorders and administration site conditions - Other, specify	1/64 (1.6%)
Irritability	3/64 (4.7%)
Non-cardiac chest pain	1/64 (1.6%)
Pain	9/64 (14.1%)
Immune system disorders
Allergic reaction	7/64 (10.9%)
Anaphylaxis	7/64 (10.9%)
Serum sickness	1/64 (1.6%)
Infections and infestations
Catheter related infection	2/64 (3.1%)
Enterocolitis infectious	1/64 (1.6%)
Esophageal infection	1/64 (1.6%)
Eye infection	2/64 (3.1%)
Gum infection	1/64 (1.6%)
Infections and infestations - Other, specify	11/64 (17.2%)
Otitis media	3/64 (4.7%)
Pharyngitis	1/64 (1.6%)
Rhinitis infective	1/64 (1.6%)
Sinusitis	1/64 (1.6%)
Skin infection	1/64 (1.6%)
Upper respiratory infection	3/64 (4.7%)
Wound infection	2/64 (3.1%)
Injury, poisoning and procedural complications
Bruising	3/64 (4.7%)
Dermatitis radiation	1/64 (1.6%)
Intraoperative neurological injury	1/64 (1.6%)
Wound dehiscence	1/64 (1.6%)
Investigations
Alanine aminotransferase increased	19/64 (29.7%)
Alkaline phosphatase increased	7/64 (10.9%)
Aspartate aminotransferase increased	21/64 (32.8%)
Blood antidiuretic hormone abnormal	2/64 (3.1%)
Blood bilirubin increased	3/64 (4.7%)
Blood corticotrophin decreased	1/64 (1.6%)
Cholesterol high	1/64 (1.6%)
Creatinine increased	3/64 (4.7%)
Investigations - Other, specify	1/64 (1.6%)
Lymphocyte count decreased	17/64 (26.6%)
Neutrophil count decreased	42/64 (65.6%)
Platelet count decreased	30/64 (46.9%)
Weight gain	1/64 (1.6%)
Weight loss	5/64 (7.8%)
White blood cell decreased	31/64 (48.4%)
Metabolism and nutrition disorders
Acidosis	10/64 (15.6%)
Anorexia	10/64 (15.6%)
Dehydration	4/64 (6.3%)
Hypercalcemia	3/64 (4.7%)
Hyperglycemia	23/64 (35.9%)
Hyperkalemia	4/64 (6.3%)
Hypermagnesemia	9/64 (14.1%)
Hypernatremia	3/64 (4.7%)
Hypoalbuminemia	7/64 (10.9%)
Hypocalcemia	9/64 (14.1%)
Hypoglycemia	8/64 (12.5%)
Hypokalemia	19/64 (29.7%)
Hypomagnesemia	4/64 (6.3%)
Hyponatremia	14/64 (21.9%)
Hypophosphatemia	10/64 (15.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/64 (3.1%)
Arthritis	1/64 (1.6%)
Back pain	3/64 (4.7%)
Generalized muscle weakness	1/64 (1.6%)
Muscle weakness upper limb	1/64 (1.6%)
Musculoskeletal and connective tissue disorder - Other, specify	1/64 (1.6%)
Neck pain	2/64 (3.1%)
Pain in extremity	5/64 (7.8%)
Nervous system disorders
Ataxia	6/64 (9.4%)
Cognitive disturbance	1/64 (1.6%)
Headache	11/64 (17.2%)
Hydrocephalus	1/64 (1.6%)
Memory impairment	1/64 (1.6%)
Nervous system disorders - Other, specify	4/64 (6.3%)
Oculomotor nerve disorder	2/64 (3.1%)
Peripheral motor neuropathy	8/64 (12.5%)
Peripheral sensory neuropathy	7/64 (10.9%)
Pyramidal tract syndrome	3/64 (4.7%)
Seizure	3/64 (4.7%)
Tremor	5/64 (7.8%)
Trigeminal nerve disorder	3/64 (4.7%)
Psychiatric disorders
Agitation	3/64 (4.7%)
Insomnia	2/64 (3.1%)
Personality change	3/64 (4.7%)
Renal and urinary disorders
Cystitis noninfective	1/64 (1.6%)
Renal and urinary disorders - Other, specify	1/64 (1.6%)
Urinary frequency	2/64 (3.1%)
Urinary tract pain	1/64 (1.6%)
Reproductive system and breast disorders
Vaginal inflammation	1/64 (1.6%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	5/64 (7.8%)
Bronchospasm	2/64 (3.1%)
Cough	9/64 (14.1%)
Epistaxis	1/64 (1.6%)
Pharyngolaryngeal pain	2/64 (3.1%)
Respiratory, thoracic and mediastinal disorders - Other, specify	4/64 (6.3%)
Voice alteration	1/64 (1.6%)
Skin and subcutaneous tissue disorders
Alopecia	10/64 (15.6%)
Dry skin	2/64 (3.1%)
Hyperhidrosis	1/64 (1.6%)
Pruritus	4/64 (6.3%)
Purpura	1/64 (1.6%)
Rash maculo-papular	8/64 (12.5%)
Skin and subcutaneous tissue disorders - Other, specify	3/64 (4.7%)
Skin hyperpigmentation	1/64 (1.6%)
Urticaria	3/64 (4.7%)
Vascular disorders
Hypertension	4/64 (6.3%)
Hypotension	2/64 (3.1%)
Vascular disorders - Other, specify	1/64 (1.6%)

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.