Trial record 2 of 901 for:    glioblastoma

Ketogenic Diet as Adjunctive Treatment in Refractory/End-stage Glioblastoma Multiforme: a Pilot Study

This study is currently recruiting participants.
Verified May 2013 by Mid-Atlantic Epilepsy and Sleep Center, LLC
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by (Responsible Party):
Mid-Atlantic Epilepsy and Sleep Center, LLC
ClinicalTrials.gov Identifier:
NCT01865162
First received: May 24, 2013
Last updated: February 19, 2014
Last verified: May 2013
  Purpose

Malignant gliomas are the most common type of brain tumor in adults. They are the second leading cause of cancer mortality in people under the age of 35 and the fourth leading cause in those under the age of 54. Standard therapy for glioblastoma multiforme (GBM) includes surgery followed by radiation and chemotherapy. Despite optimal treatment the prognosis remains poor. Patients with GBM have a median survival of approximately 10-15 months. Essentially all patients suffer recurrent disease, usually within 8 months of diagnosis. For patients with malignant glioma whose tumors recur, the median time to tumor progression is 9-13 weeks with the current standard of treatment for recurrent glioblastoma, bevacizumab (AVASTIN®). There is an urgent need for more effective therapies.

GBM cancer cells depend on glucose for energy supply and survival. When glucose levels are reduced, normal brain cells metabolize ketone bodies for energy. Brain tumor cells cannot do so. This makes the tumor cells vulnerable to death using therapies that target glucose metabolism. In brain cancer patients, high blood glucose levels are associated with reduced survival. In mice, reduction in circulating glucose levels through ketogenic diet (KD) reduces tumor growth

Ketogenic diet (KD) reduces blood glucose levels while elevating levels of ketone bodies, and may thus be beneficial in the treatment of GBM as a non-toxic metabolic therapy. KD is a high fat, low carbohydrate diet used for treatment of refractory seizures. There have been two case reports of KD use in patients with GBM showing slowing of tumor progression.

Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet that is an effective treatment of refractory epilepsy in children. The diet consists of long chain saturated triglycerides with a 3:1 or 4:1 [fat] : [protein + carbohydrate] ratio by weight, with 87-90% of calories derived from fat. The investigators have recently evaluated KD with caloric restriction of 1600 kcal /day in adults with refractory epilepsy. The diet was well tolerated. Side effects included mild nausea (n=2), mild diarrhea (n= 2), and mild constipation (n=2). No subjects stopped treatment because of side effects. Mild transient hunger was experienced by 3 subjects but there was no clinically significant hunger.

The goal of the present study is to evaluate efficacy, safety and tolerability of 4:1 KD in a small number of patients with GBM progressing or recurring after standard treatment of surgery, radiation and chemotherapy with temozolamide and, after further rescue threrapy with bevacizumab (AVASTIN®), as the first step in evaluation of therapeutic potential of KD in the treatment of GBM. This will be a small, open label pilot study. 6 patients with GBM recurring or progressing after surgery, radiation and chemotherapy (temazolamide) and after further rescue treatment with bevacizumab will be treated with 4:1 [fat]:[protein+carbohydrate] ratio, 1600 kcal/day diet. Survival, time to steroid rescue treatment and progression free survival will be compared to historical controls with life expectancy of ≤ 3 months.

The diet (KD) will consist of pre-made meals, including breakfast, lunch, dinner and two snacks, one each between breakfast and lunch and lunch and dinner, with a 2 week-long meal plan consisting of different recipes for each day of the month, with repeating 2-week-long cycles. The diet will be supplemented with vitamins, calcium and phosphorus supplements to meet the requirements of US Dietary Reference Intakes (DRI) standard. Treatment will last 6 months. Primary aims of the study will be to (1) obtain pilot data on efficacy of ketogenic diet as adjunctive treatment of treatment-refractory glioblastoma multiforme, (2) evaluate the safety of ketogenic diet as adjunctive treatment of treatment-refractory glioblastoma multiforme, and (3) evaluate tolerability of ketogenic diet as adjunctive treatment of treatment-refractory glioblastoma multiforme.

Participants will be evaluated in face-to face visit during weeks 1, 2 and 4 of the study, then monthly. Primary outcome measures will include (a) survival time and (b) time to dexamethasone rescue therapy for cerebral edema, determined by treating physician, and (c) adverse events. Secondary outcome measures will include MRI progression, treatment compliance, hunger scale scores, fasting serum glucose and BOH levels.


Condition Intervention Phase
Glioblastoma Multiforme
Other: ketogenic diet
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ketogenic Diet as Adjunctive Treatment in Refractory/End-stage Glioblastoma Multiforme: a Pilot Study

Resource links provided by NLM:


Further study details as provided by Mid-Atlantic Epilepsy and Sleep Center, LLC:

Primary Outcome Measures:
  • To evaluate the safety of ketogenic diet as adjunctive treatment of treatment-refractory glioblastoma multiforme. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    Early treatment discontinuation, treatment compliance, 7-point Licker hunger scale, fasting lipid levels and fasting serum glucose and insulin levels


Secondary Outcome Measures:
  • To obtain pilot data on efficacy of ketogenic diet as adjunctive treatment of treatment-refractory glioblastoma multiforme [ Time Frame: one year ] [ Designated as safety issue: No ]
    The secondary outcome measures will be (i) survival time and (ii) time to cerebral edema requiring steroid rescue treatment

  • To evaluate tolerability of ketogenic diet as adjunctive treatment of treatment-refractory glioblastoma multiforme. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    the incidence of treatment-emergent AEs during treatment.


Estimated Enrollment: 6
Study Start Date: January 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ketogenic diet
Treatment will consist of ketogenic diet. KD will consist of 4:1 [fat] : [protein+carbohydrate] weight ratio with 1600 kcal restriction. The diet will be supplemented with vitamins, calcium, phosphorus, zinc and selenium supplements to meet the requirements of US Dietary Reference Intakes (DRI) standard.
Other: ketogenic diet

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-65
  2. Ability and willingness to signed informed consent form.
  3. Astrocytoma grade 4 (glioblastoma multiforme, GBM, histologically confirmed, WHO criteria)
  4. Documented recurrence or progression after surgical resection/debulking, radiation and temozolamide chemotherapy.
  5. Measurable contrast-enhancing progressive or recurrent GBM by MRI imaging ≤ two weeks before screening.
  6. (a) ≥ 3months after completion of radiation; (b) 6 weeks from a nitrosourea chemotherapy; (c) ≥ weeks from a non-nitrosourea chemotherapy (all [a-c] in order to allow recovery from the potential of severe toxicity related to these treatments)
  7. Karnovsky Performance Score of 70 or more.

Exclusion Criteria:

  1. Acute intracranial or intratumoral hemorrhage > Grade 1 either by MRI or CT scan ≤2 weeks of screening. (Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study)
  2. Prior treatment with any of the following: (a) small-molecule kinase inhibitor; (b) non-cytotoxic hormonal agent; (c) KD ≤6 months of enrollment
  3. Planned continued use of glucocorticoids
  4. Anticoagulation treatment with ≥ 1 mg/day coumadin ≤ 7 days prior to screening (low-dose [≤ 1 mg/day] coumadin, heparin, and low-molecular-weight heparin are permitted
  5. Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, unstable metabolic or endocrine disturbances, renal or liver disease, past history of renal calculi, hyperuricemia, hypercalcemia, mitochondrial disease, known disorder of fatty acid metabolism, porphyria, carnitine deficiency and pancreatitis
  6. History of non-glioma malignancy other than:

    • Surgically excised non-melanoma skin cancer or in situ carcinoma of the cervix.
    • A malignancy diagnosed ≥2 years ago if the subject has had no evidence of disease for 2 years prior to screening.
  7. History of uncontrolled hyperlipidemia.
  8. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements
  9. History of human immunodeficiency virus, or hepatitis C
  10. Failure to recover from <CTCAE grade 2 toxicities related to prior therapy
  11. Pregnancy or breastfeeding
  12. Use of any investigational drug within 1 months of enrollment
  13. Inability or unwillingness of subject to give written informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01865162

Locations
United States, Maryland
MidAtlantic Epilepsy and Sleep Center Recruiting
Bethesda, Maryland, United States, 20817
Contact: Ivana Tyrlikova    301-530-9744    tyrlikovai@epilepsydc.com   
Contact: Pavel Klein, MD    301-704-4925    kleinp@epilepsydc.com   
Principal Investigator: Pavel Klein, MD         
Sponsors and Collaborators
Mid-Atlantic Epilepsy and Sleep Center, LLC
University of Pittsburgh
  More Information

No publications provided

Responsible Party: Mid-Atlantic Epilepsy and Sleep Center, LLC
ClinicalTrials.gov Identifier: NCT01865162     History of Changes
Other Study ID Numbers: maes 002
Study First Received: May 24, 2013
Last Updated: February 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mid-Atlantic Epilepsy and Sleep Center, LLC:
Glioblastoma multiforme, ketogenic diet, neoplasm

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on April 17, 2014