Clinical trial NCT02046187: Ketogenic Diet With Radiation and Chemotherapy for Newly Diagnosed Glioblastoma
Official title: Phase I/II Prospective Trial for Newly Diagnosed GBM, With Upfront Gross or Subtotal Resection, Followed by Ketogenic Diet With Radiotherapy and Concurrent Temodar(R) Chemotherapy Followed by Adjuvant Temodar(R) Chemotherapy.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Glioblastoma (GBM)
Keywords: Ketogenic Diet
Brain tumor
Glioma
Glioblastoma
Radiation
Chemotherapy
temozolomide
Lead sponsor: St. Joseph's Hospital and Medical Center, Phoenix
Sponsor class: OTHER
First posted: 2014-01-27
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to see if reducing blood sugar and increasing ketones (a metabolic product that comes from using fats for energy) can increase survival and enhance the the effects of standard radiation and chemotherapy treatments used to treat glioblastoma multiforme (GBM). These changes occur from use of a ketogenic diet. This research has 2 goals:

1. Show that patients can tolerate the diet and maintain low blood glucose and high blood ketone levels.
2. Show if this diet enhances the effectiveness of standard treatment by prolonging survival of patients with a GBM.

Detailed description: The investigators propose to offer this study to patients with newly diagnosed glioblastoma multiforme (GBM) that undergo gross total resection (GTR) or subtotal resection (STR) of their tumor. Post-operatively, these patients and their families will be instructed in the implementation of the Ketogenic Diet (KD) and it will be started as soon as possible following surgery to achieve ketosis and reduction of blood sugar. Patients will receive standard chemoradiotherapy with fractionated external beam radiation (60Gy) and concurrent oral temozolomide chemotherapy followed by 12 adjuvant cycles of temozolomide chemotherapy on a standard dose schedule. Outcome measures of the study group will be compared to historic controls in the treatment arm from the European Organization for Research and Treatment of Cancer (EORTC) temozolomide study published by Roger Stupp et al, New England Journal of Medicine, March 10, 2005.

Note: Gross Total Resection (GTR), Subtotal Resection (STR), temozolomide (Temodar), and radiation therapy are routine care for GBM and are not an investigational component of this study.

Study end-points:

Primary: Ketogenic diet (KD) tolerance and compliance in brain tumor patients. The diet will be considered tolerable if the patient chooses to remain compliant. Compliance is monitored by the dietician using self reporting of diet, blood glucose and blood ketone levels.

Secondary: Overall survival, time to recurrence, health and therapy-related quality of life. Overall survival and progression free survival will be measured and compared to the historic controls who received chemoradiotherapy in standard dose scheduling.

Laboratory correlate: Molecular/immunohistochemical analysis of tumors that do and do not respond to a KD.

Eligibility criteria: Inclusion Criteria:

* adult patients, 18 - 80 years of age,
* a single enhancing lesion of the brain with MRI appearance consistent with GBM
* Pathologic confirmation of GBM
* Zubrod Performance Scale (ZPS) \< 2
* Must be able to undergo MRI imaging with gadolinium
* Must have access to a computer and the internet (to use KetoCalculator© on-line Database)

Exclusion Criteria:

* unable to undergo MRI with gadolinium
* genetic disorders of fat metabolism
* patients receiving sodium valproate (may cause false ketone reading in urine)
* diabetes
* enrolled in another treatment trial for GBM

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 8 weeks
Secondary outcomes:
measure: overall survival
timeFrame: 2 years
measure: time to progression
timeFrame: 2 years
measure: quality of life
timeFrame: 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute at St. Joseph's Hospital and Medical Center
state: Arizona
Study officials:
affiliation: Barrow Neurological Research
name: Adrienne C Scheck, PhD
role: STUDY_CHAIR
References:
citation: Abdelwahab MG, Fenton KE, Preul MC, Rho JM, Lynch A, Stafford P, Scheck AC. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS One. 2012;7(5):e36197. doi: 10.1371/journal.pone.0036197. Epub 2012 May 1.
citation: Scheck AC, Abdelwahab MG, Fenton KE, Stafford P. The ketogenic diet for the treatment of glioma: insights from genetic profiling. Epilepsy Res. 2012 Jul;100(3):327-37. doi: 10.1016/j.eplepsyres.2011.09.022. Epub 2011 Oct 22.
citation: Stafford P, Abdelwahab MG, Kim DY, Preul MC, Rho JM, Scheck AC. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr Metab (Lond). 2010 Sep 10;7:74. doi: 10.1186/1743-7075-7-74.