Recurrent Glioblastoma
Conditions
Brief summary
This study of DSF-Cu in combination with TMZ for recurrent GBM will evaluate the antitumor effect in patients who have recurrent GBM. Patients will take DSF-Cu daily during their routine standard of care with TMZ therapy for approximately 6 months. Patients will be evaluated for response every 8 weeks. Patients will be followed up 2 years after the last dose of DSF-Cu.
Interventions
DRUGDisulfiram/Copper
Disulfiram/copper gluconate is taken three times a day.
DRUGTemozolomide (TMZ)
TMZ is given per standard of care
Sponsors
Cantex Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed GBM (WHO grade IV). * The subject must have completed RT with concurrent TMZ at least 12 weeks prior to the planned start of treatment on this study UNLESS there is pathological verification of recurrent tumor and at least 4 weeks have elapsed since the end of RT with concurrent TMZ. * Experienced first unequivocal progression of tumor by magnetic resonance imaging (MRI) \[as assessed via Radiologic Assessment in Neuro-Oncology (RANO) criteria within 3 months from the last dose of TMZ. * Karnofsky performance status (KPS) of at least 60%. * Willing to remain abstinent from consuming alcohol. * Recovered from the toxic effects of prior therapy to \< grade 2 toxicity per NCI CTCAE prior to study registration (except lymphopenia). * Meets laboratory criteria for the following parameters: ANC, platelets, hemoglobin, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, BUN and creatinine. * 11\. Females of childbearing potential must be willing to use an acceptable method of birth control (i.e., intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
Exclusion criteria
* Radiographic evidence of leptomeningeal dissemination, gliomatosis cerebri, infratentorial tumor, or disease at sites remote from the supratentorial brain. * Enrolled in another clinical trial testing a novel therapy or drug within the past 4 weeks. * Received more than one course of radiation therapy or more than a total dose of 75 Gy. * History of allergic reaction/hypersensitivity to temozolomide, dacarbazine, DSF or Cu. * Treatment with the following medications are contraindicated with DSF: metronidazole, isoniazid, dronabinol, carbocisteine, lopinavir, paraldehyde, ritonavir, sertraline, tindazole, tizanidine, atazanavir. * Fever within 3 days prior to study enrollment. * Active or severe hepatic or renal disease. * Grade 2 or higher peripheral neuropathy or ataxia per NCI CTCAE * History of idiopathic seizure disorder schizophrenia, or psychosis unrelated to glioblastoma, corticosteroid, or anti-epileptic medications. * History of Wilson's disease. * History of hemochromatosis. * Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 6 months | ORR will be defined as the percentage of patients with complete response (CR) or partial response (PR) according to the RANO criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 6 months and 12 months | Percentage of patients that are alive |
| Median Duration of Overall Survival | 14 months | Duration of overall survival for patients that are alive |
| Number of Participants With Serious Adverse Events | 14 months | Number of Participants with Grade 3 and 4 serious adverse events |
| Median Progression Free Survival | 12 months | Duration of progression free survival according to RANO criteria |
| Progression Free Survival | 6 months | Percentage of patients that are free from progressive disease per RANO criteria |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Disulfiram and Copper Gluconate Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months.
Disulfiram/Copper: Disulfiram/copper gluconate is taken three times a day.
Temozolomide (TMZ): TMZ is given per standard of care | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Disulfiram and Copper Gluconate |
|---|---|
| Age, Continuous | 61 years |
| Race/Ethnicity, Customized Black | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 21 Participants |
| Region of Enrollment United States | 23 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 14 / 23 |
| other Total, other adverse events | 0 / 23 |
| serious Total, serious adverse events | 2 / 23 |
Outcome results
Primary
Objective Response Rate
ORR will be defined as the percentage of patients with complete response (CR) or partial response (PR) according to the RANO criteria.
Time frame: 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DSF-Cu | Objective Response Rate | Complete response | 0 Participants |
| DSF-Cu | Objective Response Rate | Partial Response | 0 Participants |
Secondary
Median Duration of Overall Survival
Duration of overall survival for patients that are alive
Time frame: 14 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DSF-Cu | Median Duration of Overall Survival | 7.1 months |
Secondary
Median Progression Free Survival
Duration of progression free survival according to RANO criteria
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DSF-Cu | Median Progression Free Survival | 1.7 months |
Secondary
Number of Participants With Serious Adverse Events
Number of Participants with Grade 3 and 4 serious adverse events
Time frame: 14 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DSF-Cu | Number of Participants With Serious Adverse Events | 2 Participants |
Secondary
Overall Survival
Percentage of patients that are alive
Time frame: 6 months and 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DSF-Cu | Overall Survival | 6 months | 61 percentage of participants |
| DSF-Cu | Overall Survival | 12 months | 35 percentage of participants |
Secondary
Progression Free Survival
Percentage of patients that are free from progressive disease per RANO criteria
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DSF-Cu | Progression Free Survival | 14 percentage of participants |