A Phase I Study of Dietary Methionine Restriction and Temodar® (Temozolomide) for the Treatment of Recurrent and Progressive Glioblastoma Multiforme
Methionine is an essential amino acid. Many solid tumors depend on the methionine that is
taken in through the diet. The tumors need methionine to grow. A methionine free (or
reduced) diet may help to shrink or slow the growth of some tumors. Temozolomide is a drug
that is commonly used in the treatment of glioma. A methionine free (or reduced) diet may
increase the effectiveness of temozolomide in the treatment of glioma.
Before treatment, you will have a complete physical exam and blood (around 2 tablespoons)
will be collected for routine tests. You will have either a magnetic resonance imaging
(MRI) scan or a computed tomography (CT) scan of the brain. Women who are able to have
children must have a negative blood pregnancy test. You will then meet with a study
dietician. The dietician will give you written instructions and make a food plan based on
your needs. The instructions and food plan will help you maintain a methionine-free (or
reduced) diet during the study.
During the study, all participants will receive standard chemotherapy with temozolomide by
mouth once a day at bedtime for 7 days on Days 8 through 14 and 22 through 28, every 28
days, 4 weeks This 4-week period is called a cycle of chemotherapy. This 4 week cycle will
be repeated as long as the disease does not get worse.
During treatment, you will be asked to maintain a methionine free diet during Days 1 - 7 and
Days 15 - 21. During the periods of methionine free diet, you will consume only "shakes"
containing Hominex-2®. The Hominex-2® shakes are nutritionally complete and easy to
prepare. You will be given instructions on how to maintain this methionine-free diet.
All participants enrolled in the study will consume a methionine free diet for 1 week,
alternating with temozolomide chemotherapy for 1 week. The participants will then be
switched to a methionine "replete" diet for 1 week while taking chemotherapy. This diet and
chemotherapy schedule will be continued for as long as the treatment is effective and
tolerable. This replete diet contains methionine. The dietician will record what you eat
to make sure you are eating the right amount of methionine during this period. This 4-week
schedule will be repeated as long as you are on the study.
If you experience any intolerable side effects or the disease gets worse, you will be taken
off the study and your doctor will discuss other treatment options with you.
During treatment, you will have blood (around 1 tablespoon) collected every 2 weeks for
routine tests. Every 4 weeks for the first 16 weeks then every 8 weeks for the rest of the
study, you will have check up visits. At these visits, you will have a complete physical
exam and have blood collected (around 1 tablespoon) for routine tests. You will also have a
dietary consultation. Every 8 weeks during the study, you will have either a MRI scan or a
CT scan of the brain. If your doctor feels it is necessary, the tests may be done more
often or you may have other tests as needed for your care.
This is an investigational study. Methionine restriction diet (Hominex®-2 Amino
Acid-Modified Medical Food) has been approved by the FDA for nutrition support of children
and adults with vitamin B6-nonresponsive homocystinuria. However, its use in this study is
investigational. Temozolomide has been approved by the FDA for the treatment of brain
tumors and is commercially available. The use of this combination is experimental.
Forty-four participants will take part in this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to Disease Progression
Time to progression measured from the first day of treatment until progression is documented.
6 months (26 weeks)
Morris D. Groves, MD
M.D. Anderson Cancer Center
United States: Institutional Review Board
|U.T.M.D. Anderson Cancer Center||Houston, Texas 77030|