Bortezomib, Temozolomide, and Regional Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

• Sponsor: Jonsson Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00998010
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 24
• Location: 1
• Arm: 1
• Actual Duration (Months): 78.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bortezomib together with temozolomide and radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.

PURPOSE: This phase II trial is studying the side effects and how well bortezomib works when given together with temozolomide and regional radiation therapy in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: bortezomib + temozolomide+ radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Estimate the overall survival at 2 years of patients with newly diagnosed glioblastoma multiforme treated with bortezomib in combination with temozolomide and regional radiotherapy followed by maintenance therapy comprising bortezomib and temozolomide.

Secondary

• Investigate further the safety and tolerability of this regimen in these patients.

• Determine the molecular characterization of tumor tissue and correlate these findings with response.

OUTLINE: This is a multicenter study.

• Adjuvant chemotherapy: Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42. Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.

• Maintenance: Beginning 2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Tumor tissue samples are collected at baseline (from surgery) and periodically during study for further analysis.

After completion of study therapy, patients are followed up periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Velcade (Bortezomib) in Combination With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly-diagnosed Glioblastoma Multiforme
• Actual Study Start Date: Oct 3, 2011
• Actual Primary Completion Date: Mar 29, 2016
• Actual Study Completion Date: Apr 20, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Experimental Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42.Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5.Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Drug: bortezomib + temozolomide+ radiation therapy; Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200 centigray (cGy) daily doses to a total dose of 6000 cGy.

Outcome Measures

Primary Outcome Measures

1. Overall Survival [2 years]

   Estimate the overall survival in subjects with newly-diagnosed glioblastoma (GBM) treated with bortezomib/temozolomide/radiation followed by bortezomib/temozolomide for 24 cycles until progression is detected or for up to 24 cycles (~2 years).

Secondary Outcome Measures

1. Toxicity Assessed According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3. [2 years]

2. Time to Progression [From the completion of radiation treatment to tumor progression]

   Median time to tumor progression. Because many newly-diagnosed patients are likely not to have evaluable disease due to gross total resections. A 7-point scale was used to guide Magnetic resonance imaging (MRI) assessment to determine progression in this study. A -2 or -3 assessment will be taken as progression. The 7-point scale is listed below. complete resolution of tumor: 3 tumor definitely smaller: 2 tumor probably smaller: 1 tumor unchanged: 0 tumor probably worse: -1 tumor definitely worse: -2 new lesion: -3

3. Survival at 1 Year [1 year]

   Overall Survival at 12 months from completion of radiation treatment

4. Tumor Progression as Assessed by Magnetic Resonance Imaging (MRI) and Neurologic Exam [at 6, 12, 18 and 24 months from completion of radiation treatment.]

   MRI will be done 2 weeks after completion of radiation and then every 8 weeks. Neurologic exam to be performed every 2 weeks during radiation therapy, then every every 4 weeks after radiation is completed.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Must be >- 18 years old, with a life expectancy > 8 weeks

• Histologically confirmed intracranial glioblastoma multiforme (GBM) or gliosarcoma

• Must submit an unstained paraffin block or slides from surgical procedure

• Patients without prior treatment and with prior diagnosis of lower-grade gliomas that have been upgraded to GBM after repeated resection allowed

• At least 21 days since cranial MRI or contrast CT scan OR ≥ 96 hours since cranial MRI or contrast CT scan for patients who underwent surgical resection

• Measurable or assessable disease

• Voluntary written informed consent obtained before performance of any study related procedure not part of normal medical care.

• Karnofsky performance status > 60%

• White Blood Count (WBC) ≥ 3,000/mm^3

• absoulte neutrophil count(ANC) ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 10 g/dL (transfusion allowed)

• Bilirubin < 2.5 times upper limit of normal (ULN)

• serum glutamic-oxaloacetic transaminase (SGOT) < 2.5 times ULN

• Creatinine < 1.5 mg/dL

• Creatinine clearance ≥ 20 mL/minute

• Serum sodium > 130 mmol/L

• Negative pregnancy test

• Fertile patients must use effective contraception

• Patients on Enzyme-Inducing Antiepileptic Drugs (EIAED) must be transitioned to non- EAIED for ≥ 2 weeks

• Concurrent full-dose warfarin or its equivalent (e.g., unfractionated and/or low molecular weight heparin) allowed

Exclusion Criteria:

• peripheral neuropathy ≥ grade 2

• Myocardial infarction within the past 6 months

• New York Heart Association (NYHA) class III or IV heart failure

• Uncontrolled angina

• Severe uncontrolled ventricular arrhythmias

• Electrocardiographic evidence of acute ischemia or active conduction system abnormalities

• hypersensitivity to bortezomib, boron, or mannitol

• serious medical or psychiatric illness that would interfere with study participation including, but not limited to, any of the following:

• Ongoing or active infection requiring IV antibiotics

• Psychiatric illness and/or social situations that would limit compliance with study requirements

• Disorders associated with a significant immunocompromised state (e.g., HIV, systemic lupus erythematosus)

• history of stroke within the past 6 months

• other malignancy within the past 3 years except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy (i.e., cervical cancer), or low-risk prostate cancer after curative therapy

• significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy

• disease that will obscure toxicity or dangerously alter drug metabolism

• viral hepatitis (HBV surface antigen positive) or active hepatitis C infection

• Prior or concurrent corticosteroids, automated external defibrillator, analgesics, and other drugs to treat symptoms or prevent complications allowed

• concurrent investigational drugs that must be stopped at least 4 months prior to therapy.

• prior radiotherapy to the brain

• prior cytotoxic or noncytotoxic drug therapy or experimental drug therapy (including chemotherapy, hormonal therapy, or immunotherapy) directed against the brain tumor

• prior polifeprosan 20 with carmustine implant (Gliadel wafer)

• concurrent stereotactic radiosurgery or brachytherapy

• concurrent sargramostim

• concurrent inducers of CYP450 3A4 (e.g., enzyme-inducing anti-epileptic drugs [EIAED])

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Los Angeles	Los Angeles	California	United States	90095

Sponsors and Collaborators

• Jonsson Comprehensive Cancer Center
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Albert Lai, MD, PhD, Ronald Reagan UCLA Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 11, 2014
• Informed Consent Form - Jan 21, 2015

More Information

Publications

None provided.

• Responsible Party: Jonsson Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00998010
• Other Study ID Numbers: 11-002222; UCLA-X05303; CDR0000657015; MILLENNIUM-UCLA-X05303; 09-03-084
• First Posted: Oct 20, 2009
• Last Update Posted: Aug 28, 2020
• Last Verified: May 1, 2019

• Keywords provided by Jonsson Comprehensive Cancer Center: adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma
• Additional relevant MeSH terms: Glioblastoma; Gliosarcoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Temozolomide; Bortezomib

Study Results

Participant Flow

Recruitment Details	Recruitment period: 10/03/2011 - 4/17/2015 Location: University of California at Los Angeles, Columbia University, New York.
Pre-assignment Detail	There are no pre-assignment details to describe.

Arm/Group Title	Experimental
Arm/Group Description	Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42.Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5.Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. bortezomib + temozolomide+ radiation therapy: Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200 centigray (cGy) daily doses to a total dose of 6000 cGy.
Period Title: Overall Study
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Experimental
Arm/Group Description	Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42.Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5.Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. bortezomib + temozolomide+ radiation therapy: Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200 centigrays (cGy) daily doses to a total dose of 6000 cGy.
Overall Participants	24
Age (years) [Median (Full Range) ]
Age Range	57
Sex: Female, Male (Count of Participants)
Female	11 45.8%
Male	13 54.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 8.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 4.2%
White	18 75%
More than one race	0 0%
Unknown or Not Reported	3 12.5%
Region of Enrollment (participants) [Number]
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Estimate the overall survival in subjects with newly-diagnosed glioblastoma (GBM) treated with bortezomib/temozolomide/radiation followed by bortezomib/temozolomide for 24 cycles until progression is detected or for up to 24 cycles (~2 years).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

From completion of radiation treatment to tumor progression

Arm/Group Title	Experimental
Arm/Group Description	Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42.Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5.Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. bortezomib + temozolomide+ radiation therapy: Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200cGy daily doses to a total dose of 6000 cGy.
Measure Participants	24
Mean (95% Confidence Interval) [months]	19.1

2. Secondary Outcome

Title	Toxicity Assessed According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental
Arm/Group Description	Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42.Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5.Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. bortezomib + temozolomide+ radiation therapy: Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200cGy daily doses to a total dose of 6000 cGy.
Measure Participants	24
Grade 3 toxicity	6 25%
Grade 4 Toxicity	1 4.2%
< Grade 3 Toxicity	17 70.8%
Grade 3 toxicity	7 29.2%
Grade 4 Toxicity	0 0%
< Grade 3 Toxicity	17 70.8%
Grade 3 toxicity	0 0%
Grade 4 Toxicity	0 0%
< Grade 3 Toxicity	24 100%

3. Secondary Outcome

Title	Time to Progression
Description	Median time to tumor progression. Because many newly-diagnosed patients are likely not to have evaluable disease due to gross total resections. A 7-point scale was used to guide Magnetic resonance imaging (MRI) assessment to determine progression in this study. A -2 or -3 assessment will be taken as progression. The 7-point scale is listed below. complete resolution of tumor: 3 tumor definitely smaller: 2 tumor probably smaller: 1 tumor unchanged: 0 tumor probably worse: -1 tumor definitely worse: -2 new lesion: -3
Time Frame	From the completion of radiation treatment to tumor progression

Outcome Measure Data

Analysis Population Description

From the completion of radiation treatment to tumor progression

Arm/Group Title	Experimental
Arm/Group Description	Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42.Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5.Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. bortezomib + temozolomide+ radiation therapy: Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200cGy daily doses to a total dose of 6000 cGy.
Measure Participants	24
Median (95% Confidence Interval) [months]	6.2

4. Secondary Outcome

Title	Survival at 1 Year
Description	Overall Survival at 12 months from completion of radiation treatment
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

12 months from completion of radiation treatment to tumor progression.

Arm/Group Title	Experimental
Arm/Group Description	Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42.Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5.Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. bortezomib + temozolomide+ radiation therapy: Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200cGy daily doses to a total dose of 6000 cGy.
Measure Participants	24
Median (Full Range) [percentage of participants]	87.5 364.6%

5. Secondary Outcome

Title	Tumor Progression as Assessed by Magnetic Resonance Imaging (MRI) and Neurologic Exam
Description	MRI will be done 2 weeks after completion of radiation and then every 8 weeks. Neurologic exam to be performed every 2 weeks during radiation therapy, then every every 4 weeks after radiation is completed.
Time Frame	at 6, 12, 18 and 24 months from completion of radiation treatment.

Outcome Measure Data

Analysis Population Description

Outcome was not analyzed separately, MRI and Neurological exam were to determine the progression status, and finally reflected as Progression Free Survival and Overall Survival

Arm/Group Title	Experimental
Arm/Group Description	Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42.Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5.Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. bortezomib + temozolomide+ radiation therapy: Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200cGy daily doses to a total dose of 6000 cGy.
Measure Participants	24
Progression Free Survival rate at 6 months	54.2 225.8%
Progression Free Survival rate at 12 months	29.2 121.7%
Progression Free Survival rate at 18 months	25.0 104.2%
Progression Free Survival rate at 24 moths	25 104.2%

Adverse Events

Time Frame	Adverse Events data was collected up to 2 years from the completion of radiation treatment
Adverse Event Reporting Description	Systemic adverse event assessment occurred weekly during radiation treatment period, and on Day 1 and Day 21 of each 28-day maintenance treatment cycle, and within 30 days after administration of the last dost of study drug bortezomib.
Arm/Group Title	Experimental
Arm/Group Description	Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42.Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5.Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. bortezomib + temozolomide+ radiation therapy: Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200cGy daily doses to a total dose of 6000 cGy.
All Cause Mortality
	Experimental
	Affected / at Risk (%)	# Events
Total	15/24 (62.5%)
Serious Adverse Events
	Experimental
	Affected / at Risk (%)	# Events
Total	5/24 (20.8%)
Infections and infestations
Shingles	1/24 (4.2%)	1
Nervous system disorders
Hydrocephalus	1/24 (4.2%)	1
Craniotomy	1/24 (4.2%)	1
Respiratory, thoracic and mediastinal disorders
Pullmonary embolism	1/24 (4.2%)	1
Skin and subcutaneous tissue disorders
Rash	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	Experimental
	Affected / at Risk (%)	# Events
Total	24/24 (100%)
Blood and lymphatic system disorders
Anemia	9/24 (37.5%)	36
Leukocytopenia	9/24 (37.5%)	44
Thrombocytopenia	7/24 (29.2%)	10
Neutropenia	6/24 (25%)	30
lymphopenia	14/24 (58.3%)	107
Lymphatics Limb edema	3/24 (12.5%)	3
Lymphatics/edema Swelling on the lips	1/24 (4.2%)	1
Cardiac disorders
Cardiac/general Hypertension	1/24 (4.2%)	1
Cardiac/general Hypotension	1/24 (4.2%)	1
Cardiac arrhythmia Tachycardia	2/24 (8.3%)	2
Endocrine disorders
Cushingoid appearance	2/24 (8.3%)	2
Eye disorders
Ocular/ chalazion	2/24 (8.3%)	2
Ocular/visual Xerophtalmia/dry eyes	1/24 (4.2%)	1
Ocular/visual Blurred vision	1/24 (4.2%)	1
Conjunctivitis	2/24 (8.3%)	2
Stye on LL conjunctival border	1/24 (4.2%)	1
Gastrointestinal disorders
Poor Appetite/anorexia	6/24 (25%)	7
Nausea	11/24 (45.8%)	14
Vomiting	6/24 (25%)	9
Dehydration	1/24 (4.2%)	1
Bloating/Hemorrhoids	1/24 (4.2%)	1
Flatulence	2/24 (8.3%)	2
Constipation	8/24 (33.3%)	10
Diarrhea	1/24 (4.2%)	1
General disorders
Fatigue	17/24 (70.8%)	21
Fever	4/24 (16.7%)	5
Malaise	1/24 (4.2%)	2
Weight Loss	3/24 (12.5%)	3
Weight gain	4/24 (16.7%)	4
Insomnia	4/24 (16.7%)	4
Hypersomnia	1/24 (4.2%)	1
Chills	3/24 (12.5%)	4
Increased appetite	2/24 (8.3%)	2
Olecranon bursitis	1/24 (4.2%)	1
Dental: periodontal disease-sensitivity	1/24 (4.2%)	1
Other-VZV infection related pain	1/24 (4.2%)	1
Cramping/Bilateral Lower Extremities	1/24 (4.2%)	1
Immune system disorders
Allergy/immunology Allergic rhinitis (nasal congestion )	1/24 (4.2%)	1
Infections and infestations
Other-Pelvic infection	1/24 (4.2%)	1
Oral thrush	2/24 (8.3%)	2
Ear Infection/otitis media	1/24 (4.2%)	1
Other-Herpes zoster infection	2/24 (8.3%)	2
Metabolism and nutrition disorders
Hypoglycemia	2/24 (8.3%)	2
Elevated bilirubin	4/24 (16.7%)	16
Elevated ALP	1/24 (4.2%)	1
Elevated ALT	5/24 (20.8%)	6
Elevated AST	4/24 (16.7%)	5
Elevated LDH	1/24 (4.2%)	2
Hyperglicemia	4/24 (16.7%)	8
Hyponatremia	1/24 (4.2%)	4
Elevated CREATINIE	1/24 (4.2%)	1
Decrease GFR	1/24 (4.2%)	1
Hypercholesterolemia	1/24 (4.2%)	1
Elevated triglycerides	1/24 (4.2%)	1
Musculoskeletal and connective tissue disorders
Cramping	2/24 (8.3%)	2
meniscal tear	1/24 (4.2%)	1
Pain	2/24 (8.3%)	2
Gait/Walking	3/24 (12.5%)	5
Knee pain	1/24 (4.2%)	1
Back	2/24 (8.3%)	2
Nose	3/24 (12.5%)	3
Nervous system disorders
Encephalopathy (elevated ammonia)	1/24 (4.2%)	1
Vasogenic edema	1/24 (4.2%)	1
Seizure	5/24 (20.8%)	11
Tremor	2/24 (8.3%)	3
Mood alteration	6/24 (25%)	11
Confusion	5/24 (20.8%)	6
Memory impairment	2/24 (8.3%)	2
Cognitive disturbance	2/24 (8.3%)	2
Motor neuropathy	1/24 (4.2%)	1
Sensory neuropathy	4/24 (16.7%)	4
Hydrocephalus	2/24 (8.3%)	3
Paresthesia	3/24 (12.5%)	3
Motor weakness	3/24 (12.5%)	3
Falls	1/24 (4.2%)	1
Positional Dizziness	3/24 (12.5%)	3
voice changes Dysarthria	2/24 (8.3%)	2
Alexia	1/24 (4.2%)	1
Lack of motivation	1/24 (4.2%)	1
Difficulty with concentration	2/24 (8.3%)	2
extrapyramidal involuntary Movement Restless legs	1/24 (4.2%)	1
other- Abulia	1/24 (4.2%)	1
Aphasia	2/24 (8.3%)	2
dysphagia	1/24 (4.2%)	1
Lethargy	1/24 (4.2%)	1
Headache	14/24 (58.3%)	23
Psychiatric disorders
Personality/behavioral change	1/24 (4.2%)	1
Renal and urinary disorders
Urinary retention	1/24 (4.2%)	1
Urinary incontinence	2/24 (8.3%)	2
Urinary urgency	3/24 (12.5%)	4
Respiratory, thoracic and mediastinal disorders
Dispnea	1/24 (4.2%)	1
cough	4/24 (16.7%)	4
other-Upper respiratory tract infection	4/24 (16.7%)	4
Skin and subcutaneous tissue disorders
Injection site reaction	13/24 (54.2%)	13
Skin Rash	2/24 (8.3%)	2
skin rash-Radiodermatitis	4/24 (16.7%)	4
Skin rash- diffuse	3/24 (12.5%)	5
Wound complication	1/24 (4.2%)	1
Pruritus	6/24 (25%)	8
Other-Blepharitis	1/24 (4.2%)	1
Alopecia	3/24 (12.5%)	3
other- Skin Tears L. Forearm L. Peritibial region	1/24 (4.2%)	1
skin rash-Periorbital	1/24 (4.2%)	2
Dry Skin	1/24 (4.2%)	1
skin rash (bactrim allergy)	2/24 (8.3%)	3
Skin Rash/acne	2/24 (8.3%)	2
bruising Ecchymosis	1/24 (4.2%)	1

Limitations/Caveats

Enrolls newly diagnosed GBM patient and requires collection of frozen and paraffin tumor tissue in all study patients from original surgery. Tissues for methylated (MGHT) and isocitrate dehydrogengenotyping and correlative molecular characterization

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.