Temozolomide, Memantine Hydrochloride, Mefloquine, and Metformin Hydrochloride in Treating Patients With Glioblastoma Multiforme After Radiation Therapy
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| ClinicalTrials.gov Identifier: NCT01430351 |
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Recruitment Status :
Active, not recruiting
First Posted : September 8, 2011
Last Update Posted : April 14, 2020
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Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
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Brief Summary:
This phase I trial studies the side effects and best dose of combination chemotherapy in treating patients with glioblastoma multiforme after radiation therapy. Drugs used in chemotherapy, such as temozolomide, memantine hydrochloride, and metformin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing them or stopping them from dividing. Mefloquine may help temozolomide, memantine hydrochloride, and metformin hydrochloride kill more cancer cells by making tumor cells more sensitive to the drug. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Glioblastoma Gliosarcoma Supratentorial Glioblastoma | Drug: Mefloquine Drug: Memantine Hydrochloride Drug: Metformin Hydrochloride Drug: Temozolomide | Phase 1 |
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of temozolomide (TMZ) in combination with metformin (metformin hydrochloride) (MFRMN) and/or mefloquine (MFLOQ) and/or memantine (memantine hydrochloride) (MEMTN) in patients receiving adjuvant therapy after completing external beam radiotherapy (XRT) in combination with chemotherapy for newly diagnosed glioblastoma multiforme (GBM).
SECONDARY OBJECTIVES:
I. To determine the median progression free survival (PFS); 6, 12, and 18 month PFS; and median overall survival (OS) in patients treated with temozolomide and a combination of metformin and/or mefloquine and/or memantine.
OUTLINE: This is a dose-escalation study. Patients are randomized to 1 of 8 different treatment arms.
ARM 1: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5.
ARM 2: Patients receive temozolomide PO as in Arm 1 and memantine hydrochloride PO twice daily (BID).
ARM 3: Patients receive temozolomide PO as in Arm 1 and 30 mg mefloquine PO QD on days 1-3 of week 1 and then days 2, 4, and 6 every other week.
ARM 4: Patients receive temozolomide PO as in Arm 1 and metformin hydrochloride PO BID.
ARM 5: Patients receive temozolomide PO and memantine hydrochloride PO BID as in Arm 2, and mefloquine PO QD as in Arm 3.
ARM 6: Patients receive temozolomide PO and memantine hydrochloride PO BID as in Arm 2, and metformin hydrochloride PO BID as in Arm 4.
ARM 7: Patients receive temozolomide PO as in Arm 1, mefloquine PO QD as in Arm 3, and metformin hydrochloride PO BID as in Arm 4.
ARM 8: Patients receive temozolomide PO and memantine hydrochloride PO BID as in Arm 2, metformin hydrochloride PO BID as in Arm 4, and mefloquine PO QD as in Arm 3.
In all arms, courses repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 144 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase I Lead-In to a 2x2x2 Factorial Trial of Temozolomide, Memantine, Mefloquine, and Metformin as Post-Radiation Adjuvant Therapy of Glioblastoma Multiforme |
| Actual Study Start Date : | September 14, 2011 |
| Estimated Primary Completion Date : | September 30, 2022 |
| Estimated Study Completion Date : | September 30, 2022 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Metformin
Metformin hydrochloride
Memantine
Memantine hydrochloride
Temozolomide
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm 1 (temozolomide)
Patients receive temozolomide PO QD on days 1-5.
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Drug: Temozolomide
Given PO
Other Names:
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Experimental: Arm 2 (temozolomide, memantine hydrochloride)
Patients receive temozolomide PO as in Arm 1 and memantine hydrochloride PO BID.
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Drug: Memantine Hydrochloride
Given PO
Other Names:
Drug: Temozolomide Given PO
Other Names:
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Experimental: Arm 3 (temozolomide, mefloquine)
Patients receive temozolomide PO as in Arm 1 and 30 mg mefloquine PO QD on days 1-3 of week 1 and then days 2, 4, and 6 every other week.
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Drug: Mefloquine
Given PO Drug: Temozolomide Given PO
Other Names:
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Experimental: Arm 4 (temozolomide, metformin hydrochloride)
Patients receive temozolomide PO as in Arm 1 and metformin hydrochloride PO BID.
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Drug: Metformin Hydrochloride
Given PO
Other Names:
Drug: Temozolomide Given PO
Other Names:
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Experimental: Arm 5 (temozolomide, memantine hydrochloride, mefloquine)
Patients receive temozolomide PO and memantine hydrochloride PO BID as in Arm 2, and mefloquine PO QD as in Arm 3.
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Drug: Mefloquine
Given PO Drug: Memantine Hydrochloride Given PO
Other Names:
Drug: Temozolomide Given PO
Other Names:
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Experimental: Arm 6 (temozolomide, memantine hydrochloride, metformin)
Patients receive temozolomide PO and memantine hydrochloride PO BID as in Arm 2, and metformin hydrochloride PO BID as in Arm 4.
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Drug: Memantine Hydrochloride
Given PO
Other Names:
Drug: Metformin Hydrochloride Given PO
Other Names:
Drug: Temozolomide Given PO
Other Names:
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Experimental: Arm 7 (temozolomide, mefloquine, metformin hydrochloride)
Patients receive temozolomide PO as in Arm 1, mefloquine PO QD as in Arm 3, and metformin hydrochloride PO BID as in Arm 4.
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Drug: Mefloquine
Given PO Drug: Metformin Hydrochloride Given PO
Other Names:
Drug: Temozolomide Given PO
Other Names:
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Experimental: Arm 8 (TMZ, memantine hydrochloride, metformin, mefloquine)
Patients receive temozolomide PO and memantine hydrochloride PO BID as in Arm 2, metformin hydrochloride PO BID as in Arm 4, and mefloquine PO QD as in Arm 3.
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Drug: Mefloquine
Given PO Drug: Memantine Hydrochloride Given PO
Other Names:
Drug: Metformin Hydrochloride Given PO
Other Names:
Drug: Temozolomide Given PO
Other Names:
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Primary Outcome Measures :
- Incidence of toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: During first 28 days ]
Secondary Outcome Measures :
- Median progression free survival (PFS) [ Time Frame: Up to 4 years ]
- PFS [ Time Frame: Up to 18 months ]
- Median overall survival (OS) [ Time Frame: Up to 4 years ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients with histologically proven supratentorial glioblastoma or gliosarcoma (World Health Organization [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 have a Karnofsky performance status (KPS) of >= 60
- White blood cells (WBC) >= 3,000/ul (performed within 14 days prior to registration)
- Absolute neutrophil count (ANC) >= 1,500/mm^3 (performed within 14 days prior to registration)
- Platelet count of >= 100,000/mm^3 (performed within 14 days prior to registration)
- Hemoglobin >= 10 gm/dl (eligibility level for hemoglobin may be reached by transfusion) (performed within 14 days prior to registration)
- Serum glutamic oxaloacetic transaminase (SGOT) < 2 times upper limit of normal (ULN) (performed within 14 days prior to registration)
- Bilirubin < 2 times ULN (performed within 14 days prior to registration)
- Creatinine < 1.5 mg/dL (performed within 14 days prior to registration)
- For patients on mefloquine arm, a baseline electrocardiogram (EKG) without evidence of prolonged corrected QT (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 magnetic resonance (MR)/computed tomography (CT) is required; the same type of scan, i.e., magnetic resonance imaging (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 beta-human chorionic gonadotropin (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 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-week wash out period will be required after stopping EIAED prior to initiation of treatment
Information from the National Library of Medicine
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
Locations
| United States, Texas | |
| M D Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Marta Penas-Prado | M.D. Anderson Cancer Center |
Additional Information:
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01430351 |
| Other Study ID Numbers: |
2011-0374 NCI-2011-03038 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2011-0374 ( Other Identifier: M D Anderson Cancer Center ) P30CA016672 ( U.S. NIH Grant/Contract ) |
| First Posted: | September 8, 2011 Key Record Dates |
| Last Update Posted: | April 14, 2020 |
| Last Verified: | April 2020 |
Additional relevant MeSH terms:
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Glioblastoma Gliosarcoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Metformin Mefloquine Temozolomide Memantine |
Hypoglycemic Agents Physiological Effects of Drugs Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiparkinson Agents Anti-Dyskinesia Agents Dopamine Agents Neurotransmitter Agents Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Antimalarials Antiprotozoal Agents Antiparasitic Agents |