A Phase I lead-in to a 2x2x2 Factorial Trial of Dose Dense Temozolomide, Memantine, Mefloquine, and Metformin As Post-Radiation Adjuvant Therapy of Glioblastoma Multiforme
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. Three (3) to 6 participants will be enrolled in
each group.
- If you are in Group 1, you will take temozolomide and memantine.
- If you are in Group 2, you will take temozolomide and mefloquine.
- If you are in Group 3, you will take temozolomide and metformin.
If no intolerable side effects are seen in Groups 1-3, the next participants will be
enrolled in Groups 4-6. You will also be enrolled in a study group based on when you join
the study.
- If you are in Group 4, you will take temozolomide, memantine, and mefloquine.
- If you are in Group 5, you will take temozolomide, memantine, and metformin.
- If you are in Group 6, you will take temozolomide, mefloquine, and metformin.
If no intolerable side effects are seen in Groups 4-6, the next 12 participants will be
enrolled in Group 7. If you are in Group 7, you will take temozolomide, memantine,
mefloquine, and metformin.
The study drug doses may vary from group to group. The study doctor will discuss this with
you.
Study Drug Administration:
Each cycle is 28 days. Unless you have side effects, you will receive the same dose level
of each drug for the entire study. If you do have side effects, your dose and the doses
received by later study groups may be lowered.
You will take temozolomide by mouth 1 time each day on Days 1-5 of every cycle. You should
swallow the temozolomide capsules whole, one right after the other, without chewing them.
They should be taken on an empty stomach (at least 2 hours after and 1 hour before eating)
with about 1 cup (8 ounces) of water.
If you are in Groups 1, 4, 5, or 7, you will take memantine by mouth 2 times each day while
you are on study. It should be taken about 12 hours apart. You should swallow the
memantine capsules whole, one right after the other, without chewing them. They should be
taken on an empty stomach (at least 2 hours after and 1 hour before eating) with about 1 cup
of water.
If you are in Groups 2, 4, 6, or 7, you will take mefloquine by mouth 1 time a day on Days
1-3 of the first week, then on Monday, Wednesday, and Friday of every week after that while
you are on study. You should take mefloquine with food and about 1 cup of water.
If you are in Groups 3, 5, 6, or 7, you will take metformin by mouth 2 times a day every day
while you are on study. It should be taken about 12 hours apart. You should swallow the
metformin tablets whole, one right after the other, without chewing them. They should be
taken with food and with about 1 cup of water.
While taking multiple study drugs, you can take mefloquine and metformin together. You can
take temozolomide and memantine together. You should take mefloquine and/or metformin about
2-4 hours apart from temozolomide and/or memantine.
If you vomit while taking the study drugs, you should not make up the dose or take any more
before the next scheduled dose.
Study Visits:
Every week for the first cycle, then every 4 weeks, you will be asked about any drugs you
may be taking and if you have had any side effects.
Every week during Cycle 1, then every 2 weeks, blood (about 1-2 teaspoons) will be drawn for
routine tests.
Every 4 week during Cycles 1 and 2, then every 8 weeks:
- You will have a physical exam, including measurement of your vital signs.
- You will have a neurologic exam.
- Your performance status will be recorded.
Every 8 weeks:
-You will have an MRI scan or CT scans of the brain to check the status of the disease.
If you are in Groups 2, 4, 6, or 7, on Day 1 of Cycles 3 and 7, you will have an ECG.
At any time during the study, extra tests may be performed if the doctor thinks they are
needed for your safety. The study doctor will tell you more about any extra tests.
Length of Study:
You may take the study drugs for up to 24 cycles, as long as the doctor thinks it is in your
best interest. You will no longer be able to take the study drug if the disease gets worse,
if intolerable side effects occur, or if you are unable to follow study directions.
Long-Term Follow-Up:
After you stop taking the study drugs, the study staff will call you every 3 months to check
how you are doing. Each phone call will take about 5 minutes.
This is an investigational study. Each study drug is FDA approved and commercially
available for different uses:
- Temozolomide for the treatment of some types of brain cancer
- Memantine for the treatment of Alzheimer's disease
- Mefloquine for the treatment of malaria
- Metformin for the treatment of diabetes
The use of these drugs in combination is investigational.
Up to 144 patients will take part in this study. All will be enrolled at MD Anderson.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) Levels
MTD defined as dose where Dose Limiting Toxicity (DLT) fewer than one-third of participants experience a DLT to Metformin (MFRMN) and/or Mefloquine (MFLOQ) and/or Memantine (MEMTN) alone or in combination. MTD is dose level at which 0/3 or 1/6 patients experience DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT.
First 28 days of treatment only (cycle 1)
Yes
Marta Penas-Prado, MD
Principal Investigator
UT MD Anderson Cancer Center
United States: Institutional Review Board
2011-0374
NCT01430351
September 2011
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |