Phase I Factorial Trial of Temozolomide, Memantine, Mefloquine, and Metformin for Post-Radiation Therapy (RT) Glioblastoma Multiforme (GBM)
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ClinicalTrials.gov Identifier: NCT01430351 |
Recruitment Status
:
Active, not recruiting
First Posted
: September 8, 2011
Last Update Posted
: January 11, 2018
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The goal of this clinical research study is to find the highest tolerable dose of temozolomide in combination with memantine, mefloquine, and/or metformin that can be given to patients with glioblastoma who have already been given radiation and chemotherapy in combination. The safety of these drug combinations will also be studied.
Temozolomide is designed to kill cancer cells by damaging DNA (the genetic material of cells). The damaged DNA may cause tumor cell death.
Memantine is designed to block the activity of a protein found on the surface of cells that may control tumor growth and survival. This may stop further spread of tumor cells.
Mefloquine is designed to block a protein that helps to clean the waste in the cells and to destabilize the cell membrane. Blocking this protein may cause tumor cell death.
Metformin is designed to block a protein in tumor cells that is important in tumor growth and blood vessel development. This may cause cell death or reduce the spread of the disease.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Brain Cancer | Drug: Temozolomide Drug: Memantine Drug: Mefloquine Drug: Metformin | Phase 1 |

Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 144 participants |
Allocation: | Non-Randomized |
Intervention Model: | Factorial Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | September 2011 |
Estimated Primary Completion Date : | September 2019 |
Estimated Study Completion Date : | September 2019 |

Arm | Intervention/treatment |
---|---|
Experimental: Arm 1: TMZ + MEMTN
Temozolomide 150 m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle. Memantine 30 mg by mouth twice a day for a 28 day cycle.
|
Drug: Temozolomide
150 m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle.
Other Name: Temodar
Drug: Memantine
30 mg by mouth twice a day for a 28 day cycle.
Other Name: Namenda
|
Experimental: Arm 2: TMZ + MFLOQ
Temozolomide 150 m/m2 by mouth on alternate weeks days 1-7, 15-21 of a 28 day cycle. Mefloquine 250 mg 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 for a 28 day cycle.
|
Drug: Temozolomide
150 m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle.
Other Name: Temodar
Drug: Mefloquine
250 mg 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 for a 28 day cycle.
Other Names:
|
Experimental: Arm 3: TMZ + MFRMN
Temozolomide 150 m/m2 by mouth on alternate weeks days 1-7, 15-21 of a 28 day cycle. Metformin 1000 mg by mouth twice a day for a 28 day cycle.
|
Drug: Temozolomide
150 m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle.
Other Name: Temodar
Drug: Metformin
1000 mg by mouth twice a day for a 28 day cycle.
|
Experimental: Arm 4: TMZ + MEMTN + MFLOQ
Temozolomide 150 m/m2 by mouth on alternate weeks days 1-7, 15-21 of a 28 day cycle. Memantine 30 mg by mouth twice a day for a 28 day cycle. Mefloquine 250 mg 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 for a 28 day cycle.
|
Drug: Temozolomide
150 m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle.
Other Name: Temodar
Drug: Memantine
30 mg by mouth twice a day for a 28 day cycle.
Other Name: Namenda
Drug: Mefloquine
250 mg 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 for a 28 day cycle.
Other Names:
|
Experimental: Arm 5: TMZ + MEMTN + MFRMN
Temozolomide 150m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle. Memantine 30 mg by mouth twice a day for a 28 day cycle. Metformin 1000 mg by mouth twice a day for a 28 day cycle.
|
Drug: Temozolomide
150 m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle.
Other Name: Temodar
Drug: Memantine
30 mg by mouth twice a day for a 28 day cycle.
Other Name: Namenda
Drug: Metformin
1000 mg by mouth twice a day for a 28 day cycle.
|
Experimental: Arm 6: TMZ + MFLOQ + MFRMN
Temozolomide 150 m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle. Mefloquine 250 mg 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 for a 28 day cycle. Metformin 1000mg by mouth twice a day for a 28 day cycle.
|
Drug: Temozolomide
150 m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle.
Other Name: Temodar
Drug: Mefloquine
250 mg 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 for a 28 day cycle.
Other Names:
Drug: Metformin
1000 mg by mouth twice a day for a 28 day cycle.
|
Experimental: Arm 7: TMZ + MEMTN + MFRMN + MFLOQ
Temozolomide 150 m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle. Memantine 30 mg by mouth twice a day for a 28 day cycle. Metformin 1000 mg by mouth twice a day for a 28 day cycle. Mefloquine 250 mg 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 for a 28 day cycle.
|
Drug: Temozolomide
150 m/m2 by mouth 1 time each day on alternate weeks on Days 1-7 and Days 15-21 of every 28 day cycle.
Other Name: Temodar
Drug: Memantine
30 mg by mouth twice a day for a 28 day cycle.
Other Name: Namenda
Drug: Mefloquine
250 mg 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 for a 28 day cycle.
Other Names:
Drug: Metformin
1000 mg by mouth twice a day for a 28 day cycle.
|
- Maximum Tolerated Dose (MTD) Levels [ Time Frame: First 28 days of treatment only (cycle 1) ]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.
- Progression Free Survival (PFS) [ Time Frame: 6 months ]A brain MRI/CT will be done prior to every other cycle. A scan done at 6 months from initiation of therapy will be performed to ensure assessment of the primary endpoint.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with histologically proven supratentorial glioblastoma or gliosarcoma (WHO grade IV astrocytoma) will be eligible for this protocol. Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or gliosarcoma is made prior to any definitive treatment (radiotherapy, chemotherapy).
- All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must be registered prior to treatment with study drug.
- Patients must be >/= 18 years old.
- Patients must have a Karnofsky performance status(KPS) of >/= 60.
- Patients must have adequate bone marrow function (WBC >/= 3,000/µl, ANC >/= 1,500/mm^3, platelet count of >/= 100,000/mm^3, and hemoglobin >/= 10 gm/dl), adequate liver function (SGOT and bilirubin < 2 times ULN), and adequate renal function (creatinine < 1.5 mg/dL) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
- For patients on Mefloquine arm, a baseline EKG without evidence of prolonged QTc interval >450 ms or clinically significant arrhythmia must be obtained within 14 days prior to registration.
- A brain scan should be performed within 14 days prior to registration and steroid dosing should be stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
- Patients must have completed standard radiation therapy with concurrent TMZ and must not have evidence of progressive disease on post treatment imaging.
- Women of childbearing potential must have a negative serum or urine B-HCG pregnancy test documented within 72 hours of start of therapy.
- Patients must be registered on the study within 5 weeks of completion of concurrent chemoradiation.
Exclusion Criteria:
- Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
- For Mefloquine arm, patients with evidence of QTc interval >450 ms or clinically significant arrhythmia on baseline EKG obtained within 14 days of registration will be ineligible for protocol enrollment.
- 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, are ineligible.
- Patients must not have active infection or serious intercurrent medical illness.
- Patients must not be pregnant/breast feeding and must agree to practice adequate contraception(Acceptable forms of birth control include condom with spermicide and/or diaphragm with spermicide, and non-barrier contraception such as tubal ligation, vasectomy, oral contraceptives, implanted levonorgestrel, vaginal hormonal contraceptive ring). Patients must not be pregnant because animal studies show that both TMZ and MFLOQ are teratogenic, or there is insufficient information to estimate risk.
- Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism. Patients with a history of psychosis/schizophrenia or cardiac disease requiring beta-blocker treatment (unable to change medication to non-beta blocker), anti-malarial drugs, or quinine or quinidine will not be eligible for enrollment to a mefloquine containing arm. Patients who are on active treatment with one of the study drugs at the time of evaluation will not be eligible for enrollment to an arm containing that study drug.
- For Mefloquine arm, patients must not be on enzyme inducing anticonvulsants (EIAED); if the treating physician elects to change the medication to a non-enzyme inducing agent, a 2-weeks wash out period will be required after stopping EIAED prior to initiation of treatment.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01430351
United States, Texas | |
University of Texas MD Anderson Cancer Center | |
Houston, Texas, United States, 77030 |
Principal Investigator: | Marta Penas-Prado, MD | M.D. Anderson Cancer Center |
Additional Information:
Responsible Party: | M.D. Anderson Cancer Center |
ClinicalTrials.gov Identifier: | NCT01430351 History of Changes |
Other Study ID Numbers: |
2011-0374 NCI-2011-03038 ( Registry Identifier: NCI CTRP ) |
First Posted: | September 8, 2011 Key Record Dates |
Last Update Posted: | January 11, 2018 |
Last Verified: | January 2018 |
Studies a U.S. FDA-regulated Drug Product: | Yes | |
Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by M.D. Anderson Cancer Center:
Brain cancer Central nervous system Glioblastoma Multiforme GBM Post Radiation Therapy Post-RT External beam radiotherapy XRT Supratentorial glioblastoma Gliosarcoma |
Grade IV astrocytoma Temozolomide Temodar Memantine Namenda Mefloquine Apo-Mefloquine Lariam Metformin |
Additional relevant MeSH terms:
Glioblastoma Brain Neoplasms Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Brain Diseases |
Central Nervous System Diseases Nervous System Diseases Metformin Temozolomide Dacarbazine Memantine Mefloquine Hypoglycemic Agents Physiological Effects of Drugs Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiparkinson Agents Anti-Dyskinesia Agents |