Glioblastoma, Glioblastoma Multiforme
Conditions
Keywords
ascorbate, radiation therapy, temozolomide, ferumoxytol
Brief summary
This clinical trial evaluates adding ferumoxytol and pharamcologic ascorbate (vitamin C) to standard of care treatment of glioblastoma multiforme (a type of brain tumor) in adults. All subjects will receive ferumoxytol and pharmacologic ascorbate in addition to the standard treatment.
Detailed description
The initial, standard treatment for glioblastoma multiforme (GBM) involves maximum safe surgical resection followed by radiation combined with temozolomide (a chemotherapy pill you take by mouth). Participants in this trial will: * receive intravenous (IV) ferumoxytol the day before starting radiation, then around radiation treatments 6, 25, and 31. * receive high doses of intravenous (IV) ascorbate three times a week during the combined radiation and chemotherapy phase. * provide feedback about how they feel and their quality of life. This is done through short surveys as well as discussing with the study team.
Interventions
Ferumoxytol is an iron replacement product FDA approved for treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). This trial uses the FDA approved dosage (512 mg iron) for iron-deficiency anemia in CKD.
Intravenous ascorbate
RADIATIONExternal beam radiation therapy
Photon based, focal radiation therapy delivered consistent with national guidelines, standard for treatment of GBM.
DRUGTemozolomide
Temozolomide is a cytotoxic alkylating agent administered orally that penetrates well into the central nervous system. It is a standard-of-care treatment for GBM.
Sponsors
Bryan Allen
Holden Comprehensive Cancer Center
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willingness and ability to provide informed consent consistent with Good Clinical Practice (i.e., legally authorized representative will not be used / allowed for this study). * Stated willingness to comply with all study procedures for the duration of the study * Aged 18 years or older. * Newly diagnosed (i.e., within 6 weeks), histologically or molecularly confirmed glioblastoma or diffuse midline glioma. * Therapy to begin within 6 weeks of last surgery * Able to take oral medication * ECOG performance status of 0, 1, or 2 (KPS of \>50) * Recommended to receive temozolomide and radiation therapy * Medically fit, as determined by the prescribing oncologists, to undergo temozolomide and radiation therapy. * Agree to use of highly effective contraception from screening until at least 90 days after the last study treatment (study participant should not discontinue contraception until discussing with their treating oncologist(s)). * Not have significant co-morbid central nervous system disease, such as multiple sclerosis. * Agree to Lifestyle Considerations throughout study duration
Exclusion criteria
* Current use of the following drugs and cannot have a drug substitution or decline the drug substitution: warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide. Pharmacologic ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs. * Current use of antiretroviral drugs (e.g., nelfinavir, abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine). Pharmacologic ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs. * Insulin requirement * Requires blood glucose monitoring using finger-stick glucose checks. * Medical requirement or indication for iron supplementation (including ferumoxytol, ferrous gluconate, ferrous fumarate, or ferrous sulfate). NOTE: Over the counter, patient-elective supplementation is acceptable. * Inability to undergo MR imaging. * Pregnancy or lactation (note: potential participants should not engage in 'pump \& dump' strategy; lactation must be discontinued). * Known allergic reactions to ferumoxytol. * History of Steven's Johnson Syndrome * History of hemochromatosis. * Prior radiation treatment that would result in field overlap. For potential participants who have undergone nuclear medicine therapy, including PRRT, the study's radiation oncologist must approve study entry. * G6PD (glucose-6-phosphate dehydrogenase) deficiency * Platelet count \< 100,000 /mm3 within 21 days of first treatment * Creatinine ≥ 1.5x the institutional upper limit of normal within 21 days of the first treatment or if creatinine is elevated a creatinine clearance of \< 60 mL/(min 1.73 m2) * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring inpatient admission or a delay to start of therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Treatment with another investigational drug within 30 days prior to study treatment day 1. Imaging trials (including investigational PET or NM tracers) as well as observational trials are acceptable. * Clinical trials with an endpoint of treating the patient's cancer, including behavioral, nutritional and/or device human subject studies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Ferumoxytol-related Dose Limiting Toxicities (DLTs) | From treatment day 1 through 12 weeks after completing radiation | The recommended dose will be determined by incidence of dose limiting toxicities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimate Progression Free Survival (PFS) | From treatment day 1 to disease progression, up to 16 months post-treatment | Time (measured in months) to documented disease progression in MRI imaging as described by the RANO criteria. |
| Estimate Overall Survival (OS) | Time (measured in months) until death from any cause, up to 26 months post-treatment | Time to death from any cause. |
| Disease Response | 12 weeks post-radiation | Disease response and tumor measurements over time were assessed using Response Assessment in Neuro-Oncology (RANO) criteria in conjunction with the Neurologic Assessment in Neuro-Oncology (NANO) beginning 12 weeks after completion of radiation therapy, using radiation simulation MRI/CT as baseline. RANO disease response categories included complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Tumor measurements obtained during radiographic assessment were incorporated into the overall RANO response evaluation. |
| Number of Participants With Treatment-Related Adverse Events | Up to 36 months post-radiation | Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (v5). Treatment-related adverse events were categorized by toxicity type, including liver function, hematologic, and non-hematologic events. Participants were counted once per toxicity category if they experienced at least one treatment-related adverse event within that category during the study period. |
Countries
United States
Contacts
STUDY_DIRECTORJohn M. Buatti, MD
University of Iowa
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 6 | 4 / 6 |
| other Total, other adverse events | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 1 / 6 | 1 / 6 |
Outcome results
None listed