Temozolomide, Memantine Hydrochloride, Mefloquine, and Metformin Hydrochloride in Treating Patients With Glioblastoma Multiforme After Radiation Therapy

NCT01430351 | Terminated Phase 1

• 2 other identifiers: 2011-0374NCI-2011-03038
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma; Gliosarcoma; Supratentorial Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Incidence of toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  During first 28 days

Secondary Outcomes (3)

• Median progression free survival (PFS)

  Up to 4 years

• PFS

  Up to 18 months

• Median overall survival (OS)

  Up to 4 years

Study Arms (8)

Arm 1 (temozolomide)

EXPERIMENTAL

Patients receive temozolomide PO QD on days 1-5.

Drug: Temozolomide

Arm 2 (temozolomide, memantine hydrochloride)

EXPERIMENTAL

Patients receive temozolomide PO as in Arm 1 and memantine hydrochloride PO BID.

Drug: Memantine Hydrochloride; Drug: Temozolomide

Arm 3 (temozolomide, mefloquine)

EXPERIMENTAL

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.

Drug: Mefloquine; Drug: Temozolomide

Arm 4 (temozolomide, metformin hydrochloride)

EXPERIMENTAL

Patients receive temozolomide PO as in Arm 1 and metformin hydrochloride PO BID.

Drug: Metformin Hydrochloride; Drug: Temozolomide

Arm 5 (temozolomide, memantine hydrochloride, mefloquine)

EXPERIMENTAL

Patients receive temozolomide PO and memantine hydrochloride PO BID as in Arm 2, and mefloquine PO QD as in Arm 3.

Drug: Mefloquine; Drug: Memantine Hydrochloride; Drug: Temozolomide

Arm 6 (temozolomide, memantine hydrochloride, metformin)

EXPERIMENTAL

Patients receive temozolomide PO and memantine hydrochloride PO BID as in Arm 2, and metformin hydrochloride PO BID as in Arm 4.

Drug: Memantine Hydrochloride; Drug: Metformin Hydrochloride; Drug: Temozolomide

Arm 7 (temozolomide, mefloquine, metformin hydrochloride)

EXPERIMENTAL

Patients receive temozolomide PO as in Arm 1, mefloquine PO QD as in Arm 3, and metformin hydrochloride PO BID as in Arm 4.

Drug: Mefloquine; Drug: Metformin Hydrochloride; Drug: Temozolomide

Arm 8 (TMZ, memantine hydrochloride, metformin, mefloquine)

EXPERIMENTAL

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.

Drug: Mefloquine; Drug: Memantine Hydrochloride; Drug: Metformin Hydrochloride; Drug: Temozolomide

Interventions

Mefloquine DRUG

Given PO

Arm 3 (temozolomide, mefloquine); Arm 5 (temozolomide, memantine hydrochloride, mefloquine); Arm 7 (temozolomide, mefloquine, metformin hydrochloride); Arm 8 (TMZ, memantine hydrochloride, metformin, mefloquine)

Memantine Hydrochloride DRUG

Given PO

Also known as: Ebixia, Namenda

Arm 2 (temozolomide, memantine hydrochloride); Arm 5 (temozolomide, memantine hydrochloride, mefloquine); Arm 6 (temozolomide, memantine hydrochloride, metformin); Arm 8 (TMZ, memantine hydrochloride, metformin, mefloquine)

Metformin Hydrochloride DRUG

Given PO

Also known as: APO-Metformin, Cidophage, Dimefor, Glifage, Glucoformin, Glucophage, Glucophage ER, Metformin HCl, Riomet, Siofor

Arm 4 (temozolomide, metformin hydrochloride); Arm 6 (temozolomide, memantine hydrochloride, metformin); Arm 7 (temozolomide, mefloquine, metformin hydrochloride); Arm 8 (TMZ, memantine hydrochloride, metformin, mefloquine)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac

Arm 1 (temozolomide); Arm 2 (temozolomide, memantine hydrochloride); Arm 3 (temozolomide, mefloquine); Arm 4 (temozolomide, metformin hydrochloride); Arm 5 (temozolomide, memantine hydrochloride, mefloquine); Arm 6 (temozolomide, memantine hydrochloride, metformin); Arm 7 (temozolomide, mefloquine, metformin hydrochloride); Arm 8 (TMZ, memantine hydrochloride, metformin, mefloquine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Mefloquine; Memantine; Metformin; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Biguanides; Guanidines; Amidines; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Vinay Puduvalli

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2011
• First Posted: September 8, 2011
• Study Start: September 14, 2011
• Primary Completion: February 2, 2025
• Study Completion: February 2, 2025
• Last Updated: May 7, 2025

Record last verified: 2025-05

Locations

US (1)