Dietary Cysteine and Methionine Deprivation (CMD) in Glioma Patients

UNC Lineberger Comprehensive Cancer Center

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Conditions

Glioblastoma Multiforme

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in systemic glutathione metabolites

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.

Time frame: Baseline and up to 4 days

Secondary Outcomes

Change in systemic glutathione metabolites

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).

Time frame: Baseline and up to 6 days

Change in tumor tissue glutathione metabolites

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.

Time frame: At time of surgical resection and up to 6 days

Compliance with assigned diet regimen

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.

Time frame: Baseline and up to 6 days.

Safety of normal or Cysteine and methionine deprivation diet

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.

Time frame: Up to 30 days

Progression-Free Survival (PFS)

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.

Time frame: 1 year

Overall Survival

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