Glioblastoma MultiformePhase 1NCT00508456
Dietary Methionine Restriction Plus Temozolomide for Recurrent GBM
A Phase 1 study testing Temodar (Temozolomide) and Hominex-2 in people with Glioblastoma Multiforme, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Objectives: 1. To determine the safety, tolerability and efficacy of dietary methionine restriction for 7 days alternating with Temodar® (Temozolomide) given once a day for seven days and this repeated for up to one year in the treatment of patients with recurrent and/or progressive glioblastoma. 2. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Temodar (Temozolomide) and Hominex-2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Nov 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically proven glioblastoma multiforme (GBM).
- Unequivocal evidence of tumor recurrence or progression by MRI (or CT brain if a patient can not undergo MRI). Radiotherapy (with or without radiosensitizing drugs) must have been completed in the past. The earliest a patient can be enrolled in this study after radiotherapy is 14 days. The scan done prior to study entry documenting progression will be reviewed by the primary investigator to document tumor volume changes to provide a gross assessment of growth rate.
- Patients may have had: a) no prior chemotherapy, b) 1 prior adjuvant chemotherapy, c) 1 prior adjuvant chemotherapy followed by 1 regimen for recurrent disease, or d) 1 or 2 prior chemotherapy regimens for recurrent or progressive tumor.
- All patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of this hospital.
- Enrollment MRI or CT scan of the brain must be performed within 14 days of registration. Patients having undergone recent resection of recurrent or progressive tumor will be eligible for assessment of response as long as there is residual enhancing evaluable disease that is documented by appropriate neuroimaging and patients have recovered from the effects of surgery. Patients who after surgery have no residual enhancing disease will still be eligible for enrollment, but only assessable for time to progression, and not for response.
- Patients must have a life expectancy > 8 weeks.
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- Patients must have a Karnofsky performance status of > or = 60 (Karnofsky Performance Scale).
- Patients must have recovered from the toxic effects of prior therapy and/or at least 2 weeks from vincristine, 6 weeks from nitrosoureas, and 3 weeks from procarbazine administration. Patients must have recovered from the toxic effects of any other cytotoxic drugs which they may have received and must be 1 week from the completion of any non-cytotoxic drug therapy (e.g. 13-cis-retinoic acid, thalidomide, tamoxifen, etc.). For those patients previously treated with temozolomide, they may enroll and start the diet even 1 day after their last temozolomide dose.
- Patients must have adequate bone marrow function (ANC> or = 1,500/mm3 and platelet count of > or = 100,000/mm3), adequate liver function (SGPT and alkaline phosphatase = or <2 times normal, bilirubin = or <1.5 mg%), and adequate renal function (BUN or creatinine = or <1.5 times institutional normal) prior to starting therapy.
- All acute toxic effects (excluding neurotoxicity or alopecia) of any prior therapy must have resolved to Common Toxicity Criteria (CTC) grade = or < 1.
- Patients who are eligible for the trial and who require resection of their tumor may begin the dietary restriction component of the therapy prior to their surgery providing the time to surgery is greater than 6 days. In these patients, tissue collected at surgery will be analysed for the effects of treatment. After surgery, patients will resume an ad lib diet for anywhere from 5-14 days prior to the re-initiation of the dietary methionine restriction at the same dose level and continuance with the trial.
Who cannot join
- Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
- Patients have one or more of the following conditions may not participate in this study: a) active infection; b) pregnancy and/or disagree to practice adequate contraception; c) disease that will obscure toxicity or dangerously alter drug metabolism; d) serious intercurrent medical illness.
Trial locations and contacts
1 site in 1 country.
United States1 site
U.T.M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase I Study of Dietary Methionine Restriction and Temodar® (Temozolomide) for the Treatment of Recurrent and Progressive Glioblastoma Multiforme
Objectives:
- To determine the safety, tolerability and efficacy of dietary methionine restriction for 7 days alternating with Temodar® (Temozolomide) given once a day for seven days and this repeated for up to one year in the treatment of patients with recurrent and/or progressive glioblastoma.
- To determine the short- and long-term toxicity of dietary methionine restriction combined with Temodar® in glioblastoma patients.
- To measure and correlate patients' tumor responses and progression-free survival with: serum methionine and peripheral blood lymphocyte methylation levels. In any patient undergoing surgery, to measure tumor alkylguanyl transferase (AGT) and methionine levels and compare to control specimens.
Read the detailed description
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.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Temodar (Temozolomide), Hominex-2
- Keywords
- Glioblastoma Multiforme, Methionine Restriction, Hominex-2, Methionine Restriction Diet, Hominex-2 Amino Acid-Modified Medical Food, Temozolomide, Temodar
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temodar (Temozolomide)Drug
150 mg/m^2 orally once a day for 7 consecutive days (days 8 through 15).
Hominex-2Dietary supplement
Also called Hominex-2® shakes, Methionine restriction diet, Hominex®-2 Amino Acid-Modified Medical Food
Methionine free diet during Days 1 - 7 and Days 15 - 21 by consuming only "shakes" containing Hominex-2®.
| Study group | Role | What they receive |
|---|---|---|
| Hominex®-2 + Temodar® | Experimental | Dietary Methionine Restriction (Hominex®-2) Days 1-7 and 15-21 + Temodar® 150 mg/m^2 orally Days 8-15 Receives: Drug: Temodar (Temozolomide); Dietary Supplement: Hominex-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Disease Progression
Time to progression measured from the first day of treatment until progression is documented.
Measured: 6 months (26 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2007 (estimated)
- Study startAug 2004
- Primary completionNov 2008
- Study completionNov 2008
Why it stopped: Low Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Morris D. Groves, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00508456
- Sponsor's protocol ID
- ID03-0066
- Status last verified
- Jan 2012
- First submitted
- 27 Jul 2007
- Last updated
- 16 Jan 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Dietary Methionine Restriction and Temodar® (Temozolomide) for the Treatment of Recurrent and Progressive Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00508456
- Acronym / sponsor ID
- ID03-0066
- Conditions
- Glioblastoma Multiforme
- Keywords
- Glioblastoma Multiforme, Methionine Restriction, Hominex-2, Methionine Restriction Diet, Hominex-2 Amino Acid-Modified Medical Food, Temozolomide, Temodar
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accrual
- Enrolment
- 18 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Aug 2004
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 30 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objectives:
- To determine the safety, tolerability and efficacy of dietary methionine restriction for 7 days alternating with Temodar® (Temozolomide) given once a day for seven days and this repeated for up to one year in the treatment of patients with recurrent and/or progressive glioblastoma.
- To determine the short- and long-term toxicity of dietary methionine restriction combined with Temodar® in glioblastoma patients.
- To measure and correlate patients' tumor responses and progression-free survival with: serum methionine and peripheral blood lymphocyte methylation levels. In any patient undergoing surgery, to measure tumor alkylguanyl transferase (AGT) and methionine levels and compare to control specimens.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hominex®-2 + Temodar® | Experimental | Drug: Temodar (Temozolomide), Dietary Supplement: Hominex-2Dietary Methionine Restriction (Hominex®-2) Days 1-7 and 15-21 + Temodar® 150 mg/m^2 orally Days 8-15 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically proven glioblastoma multiforme (GBM).
- Unequivocal evidence of tumor recurrence or progression by MRI (or CT brain if a patient can not undergo MRI). Radiotherapy (with or without radiosensitizing drugs) must have been completed in the past. The earliest a patient can be enrolled in this study after radiotherapy is 14 days. The scan done prior to study entry documenting progression will be reviewed by the primary investigator to document tumor volume changes to provide a gross assessment of growth rate.
- Patients may have had: a) no prior chemotherapy, b) 1 prior adjuvant chemotherapy, c) 1 prior adjuvant chemotherapy followed by 1 regimen for recurrent disease, or d) 1 or 2 prior chemotherapy regimens for recurrent or progressive tumor.
- All patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of this hospital.
- Enrollment MRI or CT scan of the brain must be performed within 14 days of registration. Patients having undergone recent resection of recurrent or progressive tumor will be eligible for assessment of response as long as there is residual enhancing evaluable disease that is documented by appropriate neuroimaging and patients have recovered from the effects of surgery. Patients who after surgery have no residual enhancing disease will still be eligible for enrollment, but only assessable for time to progression, and not for response.
Key exclusion criteria (2 listed)
- Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
- Patients have one or more of the following conditions may not participate in this study: a) active infection; b) pregnancy and/or disagree to practice adequate contraception; c) disease that will obscure toxicity or dangerously alter drug metabolism; d) serious intercurrent medical illness.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Temodar (Temozolomide)150 mg/m^2 orally once a day for 7 consecutive days (days 8 through 15). | Drug | Hominex®-2 + Temodar® |
| Hominex-2Also: Hominex-2® shakes, Methionine restriction diet, Hominex®-2 Amino Acid-Modified Medical FoodMethionine free diet during Days 1 - 7 and Days 15 - 21 by consuming only "shakes" containing Hominex-2®. | Dietary supplement | Hominex®-2 + Temodar® |
Primary outcome
Time to Disease Progression
Time frame: 6 months (26 weeks)
Time to progression measured from the first day of treatment until progression is documented.
Results and safety
The study was stopped early (reason given: Low Accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2012.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Morris D. Groves, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Temodar (Temozolomide) and Hominex-2 in people with Glioblastoma Multiforme, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low Accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Disease Progression (time frame: 6 months (26 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2012.