Glioblastoma Multiforme, Recurrent Glioma
Conditions
Keywords
glutathione metabolites, dietary restriction of cysteine, dietary restriction of methionine, radiation, surgery
Brief summary
This pilot study looks at how certain diet changes affect the body in patients with recurrent brain tumors (glioma) who are planning to have standard treatment like radiation or surgery. Up to 30 patients will be randomly assigned to either a regular diet or a special diet that limits two nutrients (cysteine and methionine) for 2, 4, or 7 days before their treatment. Patients will be monitored for side effects using blood tests and questionnaires, and patients will keep a diary to track how well they follow the diet. Blood and urine samples will be used to see how the diet affects the body. Tumor samples (from surgery) will help researchers study how the cancer cells behave, and stool samples will be used to look at gut bacteria. This is a randomized, blinded interventional pilot study to measure glutathione metabolite levels with a cysteine/methionine deprivation (CMD) diet in glioma patients. A menu of pre-prepared meals will be provided to subjects that consist of either a control diet or a CMD diet. The CMD diet will be implemented simultaneously in 2 cohorts of participants with recurrent glioma. The primary objective will be to measure the metabolic state of glioblastome multiforme tumor cells through dietary restriction of the sulfur-containing amino acids (SAA), cysteine/cystine and methionine. Patient from cohort A can later be included in Cohort B if applicable. Patients will be followed for progression free survival and overall survival for up to 1 year, or until they discontinue or are removed from the study for exploratory endpoints.
Interventions
OTHERNormal diet
Participants receive normal diet.
OTHERCysteine/methionine deprivation (CMD) diet for 2 days
Participants receive cysteine/methionine deprivation (CMD) diet for 2 days.
OTHERCysteine/methionine deprivation (CMD) diet for 4 days
receive cysteine/methionine deprivation (CMD) diet for 4 days.
Sponsors
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
In order to participate in this study a subject must meet all of the eligibility criteria outlined below. Eligibility must be maintained up until the point at which the subject receives treatment for the subject to be considered eligible for treatment. Inclusion Criteria: * Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. * Subjects is willing and able to comply with study procedures based on the judgement of the investigator. * Age ≥ 18 years at the time of consent. * Karnofsky Performance Status of ≥ 60 assessed at diagnosis
Exclusion criteria
* Active infection requiring systemic therapy. * Any active disease that may be associated with unacceptable anesthetic/operative risk. * Pregnant or breastfeeding * Subjects with prior brain metastasis. * Transfusion within 7 days of diet initiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in systemic glutathione metabolites | Baseline and up to 4 days | Systemic glutathione metabolite levels in blood and urine will be assessed before and after a 2-day randomized assigned diet (normal or Cysteine and methionine deprivation (CMD)) diet. Measurements will be obtained using laboratory assays and Magnetic resonance (MR) spectroscopy. Analyses will be conducted overall and stratified by patients scheduled for standard-of-care (SOC) radiation therapy or surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in systemic glutathione metabolites | Baseline and up to 6 days | Glutathione metabolite levels in blood and urine will be measured before and after assigned diet (normal or Cysteine and methionine deprivation (CMD)) diet. regimen using laboratory assays and Magnetic resonance (MR) spectroscopy. The pre-diet assessment will occur after a 2-day fast, and the post-diet assessment will occur after 4 days on the assigned diet (CMD or control). |
| Change in tumor tissue glutathione metabolites | At time of surgical resection and up to 6 days | Local tumor tissue metabolite levels will be assessed in resected glioma specimens from patients in the surgical cohort following assigned diet (normal or Cysteine and methionine deprivation (CMD) for 2 days and 4 days) diet. regimens. Metabolite levels will be measured using laboratory assays and Magnetic resonance (MR) spectroscopy to evaluate changes associated with acute CMD exposure. |
| Compliance with assigned diet regimen | Baseline and up to 6 days. | The proportion of patients who achieve 100% compliance with their assigned diet (normal or Cysteine and methionine deprivation (CMD)) diet. regimen will be assessed. The numerator is the number of patients with complete diet adherence, and the denominator is the total number of patients randomized to each diet. Compliance will be calculated separately for the 2-day and 4-day CMD regimens. |
| Safety of normal or Cysteine and methionine deprivation diet | Up to 30 days | Safety will be evaluated in patients receiving normal or Cysteine and methionine deprivation (CMD) 2-day or 4-day diet from randomization through 30 days after standard-of-care surgery or radiation. Assessments will include hematology, serum chemistry, and adverse events graded per The NCI Common Terminology Criteria for Adverse Events (AE) is a descriptive terminology (CTCAE). CTCAE is a grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. |
| Progression-Free Survival (PFS) | 1 year | PFS will be assessed in patients randomized to each diet regimen following surgery or radiation. PFS is defined as the time from the start of the prescribed diet to disease progression or death from any cause, whichever occurs first. Data will be obtained via medical record abstraction at 1 year. |
| Overall Survival | 1 year | OS will be described for evaluable a patients randomized to each diet regimen following surgery or radiation. OS will be defined as the time from the start of the prescribed diet to death from any cause and obtained via medical record abstraction at 1 year |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDominique Higgins, MD, PhD
UNC Lineberger Comprehensive Cancer Center
Outcome results
None listed