Disulfiram/Copper With Concurrent Radiation Therapy and T... | NCT02715609

NCT02715609

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose escalation - dose level 2)	Experimental	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.	Drug: Disulfiram Drug: Copper Gluconate Procedure: Surgery Radiation: Radiation Drug: Temozolomide
Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose escalation - dose level 3)	Experimental	Disulfiram (DSF) dose level 3=375mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.	Drug: Disulfiram Drug: Copper Gluconate Procedure: Surgery Radiation: Radiation Drug: Temozolomide

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Disulfiram	Drug		Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose escalation - dose level 2) Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose escalation - dose level 3) Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose expansion)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Tolerated Dose (MTD) of DSF (Dose-escalation Phase Only)	The maximum tolerated dose (MTD) of DSF is defined as the dose level at which 20% of the cohort experience dose-limiting toxicity (DLT) within 18 weeks from start of RT (or 12 weeks from the end of RT if there is a delay in RT). MTD is assessed from the first dose of DSF in combination with TMZ and RT; patients will not be assessed for DLT during the pre-surgery period when they are receiving the lead-in doses of DSF. A DLT is defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications/TMZ which occurs within 18 weeks following the first dose of DSF with RT+TMZ (corresponding to approximately 6 weeks during RT and 12 weeks after RT)	Estimated to be 2 years and 28 weeks
Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)		1 year
Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)		2 years
Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)		3 years
Mean Overall Survival (Dose-expansion Phase Only)		Through completion of follow-up (up to 5 years)

Secondary Outcomes

Measure	Description	Time Frame
Toxicity of DSF When Given Concurrently With Radiation Therapy and Temozolomide as Measured by the Grade and Frequency of Grade 2 or Greater Adverse Events Related to DSF	The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.	Through completion of DSF treatment (up to 38 weeks)

Other Outcomes

Measure	Description	Time Frame
Rate of Pseudo-progression (PsP)	-Pseudoprogression is defined as a transient increase of tumor after chemoradiotherapy that subsequently stabilizes without a change of therapy	Through completion of follow-up (up to 5 years)
Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Glutamine Levels in Plasma and Tumor Tissues

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of GBM or its histological variants (WHO grade IV). Patients who are participating in the optional preoperative pharmacokinetic study, may have presumed GBM based on clinical/radiological findings. However, patient must have histologically confirmed GBM before continuing to receive DSF with concurrent RT/TMZ.
Expansion Cohort: must have a diagnosis of GBM (or its histological variants) with IDH, BRAF, or NF1 mutations. Confirmation of these mutations may be either by immunohistochemistry or next-generation sequencing
At least 18 years of age.
Karnofsky performance status (KPS) of at least 60%
For patients who will participate in the optional pre-operative DSF pharmacokinetic study, they should be eligible for surgical resection for which at least 0.2 cubic cm or approximately 200 mg of tumor will be removed in additional to tumor specimen required for pathology evaluation. Patients enrolled after undergoing surgical resection or biopsy with histologically confirmed GBM are not required to meet this point of inclusion.
Eligible for and planning to receive standard fractionated RT with concurrent TMZ.
Willing to remain abstinent from consuming alcohol while on DSF.
Willing to defer definitive surgery for one week while taking DSF and Cu. Patients who declined the optional pre-operative pharmacokinetic study or enrolled after undergoing surgical resection or biopsy with histologically confirmed GBM are not required to meet this point of inclusion.
Meets the following laboratory criteria:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin > 10.0 g/dL (transfusion and/or ESA allowed)
- Total bilirubin ≤ 2x institutional upper limit of normal (ULN)
- AST and ALT < 3 x ULN
- Serum creatinine < 1.5 x ULN or creatinine clearance > 50 mL/min (by Cockcroft-Gault)
Females of childbearing potential (defined as a female who is non-menopausal or surgically sterilized) must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Able to take oral medication.
Able to understand and willing to sign an IRB-approved written informed consent document (legally authorized representative permitted).

Exclusion Criteria:

Receipt of any other investigational agents within 14 days prior to study treatment
Enrolled on another clinical trial testing a novel therapy or drug.
History of allergic reaction to DSF or Cu.
Treatment with the following medications are contraindicated with DSF when taken within 7 days prior to the first dose of DSF + Cu: metronidazole, isoniazid, dronabinol, carbocisteine, lopinavir, paraldehyde, ritonavir, sertaline, tindazole, tixanidine, atazanavir. (Note: the following medications are not contraindicated but should be cautioned if taking concurrently with DSF: warfarin, phenytoin, theophylline, chlorzoxazone, chlordiazepoxide, diazepam. If the patient is taking warfarin, INR should be monitored closely. If the patient has to remain on phenytoin, its serum concentration and response should be monitored closely.
Active or severe hepatic, cardiovascular, or cerebrovascular disease, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
History of idiopathic seizure disorder, psychosis, or schizophrenia.
History of Wilson's disease or family member with Wilson's disease.
History of hemochromatosis or family member with hemochromatosis.
Pregnant and breastfeeding women will be excluded because of the known teratogenic effect of RT and the unknown effect of TMZ and DSF on fetal development. Women of childbearing potential must have a negative pregnancy test within 14 days of initiation of treatment.

Contacts/Locations Module

Name	Affiliation	Role
Jiayi Huang, M.D.	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Washington University School of Medicine		St Louis	Missouri	63110	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38768767	Derived	Huang J, Campian JL, DeWees TA, Skrott Z, Mistrik M, Johanns TM, Ansstas G, Butt O, Leuthardt E, Dunn GP, Zipfel GJ, Osbun JW, Abraham C, Badiyan S, Schwetye K, Cairncross JG, Rubin JB, Kim AH, Chheda MG. A Phase 1/2 Study of Disulfiram and Copper With Concurrent Radiation Therapy and Temozolomide for Patients With Newly Diagnosed Glioblastoma. Int J Radiat Oncol Biol Phys. 2024 Nov 1;120(3):738-749. doi: 10.1016/j.ijrobp.2024.05.009. Epub 2024 May 19.

Label	URL
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2)	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jan 24, 2025

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2)	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
BG001	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 3)	Disulfiram (DSF) dose level 3=375mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
BG002	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Expansion)	Surgery performed per routine clinical care. Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. Disulfiram (DSF) daily (250 mg) and Copper (Cu) three times daily during chemoradiotherapy. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles. If a patient develops recurrent tumor during follow-up and plans to undergo another resection, he/she may opt for an optional preoperative DSF study prior to salvage surgery.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0009 BG00110 BG00216 BG00335

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00056(22 to 72) BG00148(23 to 78) BG00251.5(29 to 73) BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0003 BG0018 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0009 BG00110 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Tolerated Dose (MTD) of DSF (Dose-escalation Phase Only)

The maximum tolerated dose (MTD) of DSF is defined as the dose level at which 20% of the cohort experience dose-limiting toxicity (DLT) within 18 weeks from start of RT (or 12 weeks from the end of RT if there is a delay in RT). MTD is assessed from the first dose of DSF in combination with TMZ and RT; patients will not be assessed for DLT during the pre-surgery period when they are receiving the lead-in doses of DSF.
A DLT is defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications/TMZ which occurs within 18 weeks following the first dose of DSF with RT+TMZ (corresponding to approximately 6 weeks during RT and 12 weeks after RT)

One participant was not evaluable in dose escalation - dose level 2 as the participant did not receive DSF + RT + TMZ. This outcome measure is not for dose expansion portion of the trial.

Posted

Number

Estimated to be 2 years and 28 weeks

ID	Title	Description
OG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2 & 3)	Disulfiram (DSF) dose level 2=250mg, dose level 3=375mg Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
OG001	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Expansion)	Surgery performed per routine clinical care. Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. Disulfiram (DSF) daily (250 mg) and Copper (Cu) three times daily during chemoradiotherapy. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles. If a patient develops recurrent tumor during follow-up and plans to undergo another resection, he/she may opt for an optional preoperative DSF study prior to salvage surgery.

Units	Counts
Participants	OG00018 OG0010

Title

Denominators

Categories

Title	Measurements
	OG000375

Primary

Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)

This outcome measure is for participants enrolled in dose expansion only.

Posted

Number

percentage of participants-Kaplan Meier

1 year

ID	Title	Description
OG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2)	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
OG001	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 3)	Disulfiram (DSF) dose level 3=375mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.

Primary

Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)

This outcome measure is for participants enrolled in dose expansion only.

Posted

Number

percentage of participants-Kaplan Meier

2 years

ID	Title	Description
OG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2)	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
OG001	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 3)	Disulfiram (DSF) dose level 3=375mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.

Primary

Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)

This outcome measure is for participants enrolled in dose expansion only.

Posted

Number

percentage of participants-Kaplan Meier

3 years

ID	Title	Description
OG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2)	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
OG001	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 3)	Disulfiram (DSF) dose level 3=375mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.

Primary

Mean Overall Survival (Dose-expansion Phase Only)

This outcome measure is for participants enrolled in dose expansion only.

Posted

Mean

95% Confidence Interval

months

Through completion of follow-up (up to 5 years)

ID	Title	Description
OG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2)	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
OG001	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 3)	Disulfiram (DSF) dose level 3=375mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.

Secondary

Toxicity of DSF When Given Concurrently With Radiation Therapy and Temozolomide as Measured by the Grade and Frequency of Grade 2 or Greater Adverse Events Related to DSF

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

Posted

Count of Participants

Participants

Through completion of DSF treatment (up to 38 weeks)

ID	Title	Description
OG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2)	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
OG001	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 3)	Disulfiram (DSF) dose level 3=375mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.

Secondary

Intratumor and Plasma Concentration of DSF Metabolite (Ditiocarb-copper Complex)

Will be determined using mass spectrometer

Only 3 patients had tumor resection after preoperative DSF/Cu administration.

Posted

Number

ng/mL

At the time of surgery (day 4)

ID	Title	Description
OG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2)	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
OG001	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Expansion)	Surgery performed per routine clinical care. Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. Disulfiram (DSF) daily (250 mg) and Copper (Cu) three times daily during chemoradiotherapy. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles. If a patient develops recurrent tumor during follow-up and plans to undergo another resection, he/she may opt for an optional preoperative DSF study prior to salvage surgery.

Secondary

Mean Progression-free Survival (PFS)

Will be determined from the first day of RT to the time of tumor progression or death, whichever occurs first. Tumor progression will be determined using the RANO criteria.

Posted

Mean

95% Confidence Interval

months

Through completion of follow-up (up to 5 years)

ID	Title	Description
OG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2)	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
OG001	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 3)	Disulfiram (DSF) dose level 3=375mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.

Other Pre-specified

Rate of Pseudo-progression (PsP)

-Pseudoprogression is defined as a transient increase of tumor after chemoradiotherapy that subsequently stabilizes without a change of therapy

Not Posted

Through completion of follow-up (up to 5 years)

Participants

Other Pre-specified

Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Glutamine Levels in Plasma and Tumor Tissues

Not Posted

Week 6

Participants

Other Pre-specified

Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Glutamate Levels in Plasma and Tumor Tissues

Not Posted

Week 6

Participants

Other Pre-specified

Time to Tumor Progression (TTP) (Dose-escalation Phase Only)

-≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids. The absolute increase in any dimension must be at least 5mm when calculating the products

Significant increase in T2/FLAIR nonenhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy not caused by comorbid events
Any new measureable lesion
Clear clinical deterioration not attributable to other causes apart from the tumor (e.g. seizures, medication adverse effects, complications of therapy, cerebrovascular events, infection, and so on) or changes in corticosteroid dose
Failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease

Not Posted

Through completion of follow-up (up to 5 years)

Participants

Other Pre-specified

Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Aspartate Levels in Plasma and Tumor Tissues

Not Posted

Week 6

Participants

Other Pre-specified

Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Glucose Levels in Plasma and Tumor Tissues

Not Posted

Week 6

Participants

Other Pre-specified

Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Lactate Levels in Plasma and Tumor Tissues

Not Posted

Week 6

Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 2)	Disulfiram (DSF) dose level 2=250mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.	5	9	3	9	9	9
EG001	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Escalation - Dose Level 3)	Disulfiram (DSF) dose level 3=375mg. Preoperative DSF/Copper (CU) x 3 days (optional) Surgery performed per routine clinical care. After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study). Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.	5	10	5	10	10	10
EG002	Disulfiram, Copper, Surgery, Radiation Therapy, Temozolomide (Dose Expansion)	Surgery performed per routine clinical care. Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions. Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care. Disulfiram (DSF) daily (250 mg) and Copper (Cu) three times daily during chemoradiotherapy. 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles. If a patient develops recurrent tumor during follow-up and plans to undergo another resection, he/she may opt for an optional preoperative DSF study prior to salvage surgery..	9	16	7	16	16	16

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Death NOS	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0010 affected10 at risk EG0024 affected16 at risk
Fever	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Lung infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Alanine aminotransferase increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Aspartate aminotransferase increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0021 affected16 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0021 affected16 at risk
Ataxia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Confusion	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk
Headache	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Lethargy	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Seizure	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0021 affected16 at risk
Somnolence	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Stroke	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk
Delirium	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0013 affected10 at risk EG0020 affected16 at risk
Elevated heart rate	Cardiac disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Ear pain	Ear and labyrinth disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Hypothyroidism	Endocrine disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Blurred vision	Eye disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Diminished peripheral vision - left side	Eye disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Eye pain	Eye disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Right peripheral field cut	Eye disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Abdominal pain	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Constipation	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0005 affected9 at risk EG0012 affected10 at risk EG0024 affected16 at risk
Dental abscess	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected9 at risk EG0012 affected10 at risk EG0022 affected16 at risk
Dyspepsia	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0012 affected10 at risk EG0020 affected16 at risk
Dysphagia	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0012 affected10 at risk EG0020 affected16 at risk
Fecal incontinence	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0012 affected10 at risk EG0021 affected16 at risk
Flatulence	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Mucositis oral	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Nausea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0009 affected9 at risk EG0014 affected10 at risk EG0022 affected16 at risk
Vomiting	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected9 at risk EG0011 affected10 at risk EG0021 affected16 at risk
Chills	General disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Edema face	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Edema hands	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Edema limbs	General disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Fatigue	General disorders	CTCAE (4.0)	Systematic Assessment	EG0008 affected9 at risk EG0017 affected10 at risk EG00211 affected16 at risk
Fever	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Gait disturbance	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0022 affected16 at risk
Infusion related reaction	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Localized edema	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Pain	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0011 affected10 at risk EG0021 affected16 at risk
Cold	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Ear infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk
Skin infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Urinary tract infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk
Yeast infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Bruising	Injury, poisoning and procedural complications	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Fall	Injury, poisoning and procedural complications	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0012 affected10 at risk EG0020 affected16 at risk
Alanine aminotransferase increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0004 affected9 at risk EG0013 affected10 at risk EG0022 affected16 at risk
Alkaline phosphatase increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Aspartate aminotransferase increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0011 affected10 at risk EG0021 affected16 at risk
CD4 lymphocytes decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Creatinine increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Lymphocyte count decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0006 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Neutrophil count decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0021 affected16 at risk
Platelet count decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0005 affected9 at risk EG0012 affected10 at risk EG0020 affected16 at risk
Weight loss	Investigations	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
White blood cell decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0011 affected10 at risk EG0021 affected16 at risk
Diabetes mellitus-steroid induced	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Hypercalcemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0012 affected10 at risk EG0020 affected16 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0012 affected10 at risk EG0020 affected16 at risk
Hypocalcemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0012 affected10 at risk EG0020 affected16 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0013 affected10 at risk EG0020 affected16 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Arthritis	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Back pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Flank pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected9 at risk EG0011 affected10 at risk EG0022 affected16 at risk
Knee pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Muscle cramp	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Muscle spasm	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Muscle weakness left-sided	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0013 affected10 at risk EG0021 affected16 at risk
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Muscle weakness right-sided	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk
Myalgia	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected9 at risk EG0012 affected10 at risk EG0020 affected16 at risk
Neck pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Ataxia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0013 affected10 at risk EG0025 affected16 at risk
Cognitive disturbance - aphasia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk
Dizziness	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0008 affected9 at risk EG0012 affected10 at risk EG0022 affected16 at risk
Dysgeusia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Dysphasia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0012 affected10 at risk EG0022 affected16 at risk
Facial muscle weakness	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Headache	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0006 affected9 at risk EG0016 affected10 at risk EG0023 affected16 at risk
Impaired balance	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Lethargy	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Lightheadedness	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Memory impairment	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0006 affected9 at risk EG0012 affected10 at risk EG0020 affected16 at risk
Movements involuntary	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Paresthesia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Peripheral motor neuropathy	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0013 affected10 at risk EG0022 affected16 at risk
Peripheral sensory neuropathy	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0012 affected10 at risk EG0021 affected16 at risk
Presyncope	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk
Seizure	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0023 affected16 at risk
Somnolence	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Tremor	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0005 affected9 at risk EG0014 affected10 at risk EG0020 affected16 at risk
Tunnel vision	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Agitation	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Anxiety	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected9 at risk EG0012 affected10 at risk EG0021 affected16 at risk
Confusion	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected9 at risk EG0013 affected10 at risk EG0021 affected16 at risk
Delirium	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0021 affected16 at risk
Depression	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0005 affected9 at risk EG0012 affected10 at risk EG0020 affected16 at risk
Insomnia	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected9 at risk EG0013 affected10 at risk EG0021 affected16 at risk
Irritability	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Mania	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Bladder spasm	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Dribbling with urination	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Urinary frequency	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Urinary incontinence	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0012 affected10 at risk EG0023 affected16 at risk
Urinary tract obstruction	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Urinary tract pain	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Urinary urgency	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Erectile dysfunction	Reproductive system and breast disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0011 affected10 at risk EG0021 affected16 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Alopecia	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0006 affected9 at risk EG0011 affected10 at risk EG0022 affected16 at risk
Dry skin	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected9 at risk EG0011 affected10 at risk EG0020 affected16 at risk
Pruritus	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Scalp pain	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0020 affected16 at risk
Skin ulceration	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected9 at risk EG0010 affected10 at risk EG0021 affected16 at risk

ID	Term
D005909	Glioblastoma

Ancestor Terms

ID	Term
D001254	Astrocytoma
D005910	Glioma
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009375	Neoplasms, Glandular and Epithelial
D009380	Neoplasms, Nerve Tissue

ID	Term
D004221	Disulfiram
D005942	Gluconates
D003300	Copper
D013514	Surgical Procedures, Operative
D011827	Radiation
D000077204	Temozolomide

Ancestor Terms

ID	Term
D004050	Ditiocarb
D013859	Thiocarbamates
D002219	Carbamates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D004220	Disulfides
D013440	Sulfides
D013457	Sulfur Compounds
D013400	Sugar Acids
D006880	Hydroxy Acids
D002241	Carbohydrates
D019216	Metals, Heavy
D004602	Elements
D007287	Inorganic Chemicals
D028561	Transition Elements
D008670	Metals
D055585	Physical Phenomena
D003606	Dacarbazine
D014226	Triazenes
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds