MDACC Study Summary 2011-0374

Study Summary
No. 2011-0374:.......Brain; CNS......Marta Penas-Prado......Neuro Oncology

Study Summary Title



Study Summary Number:	2011-0374

Study 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

Physician

New Patient Referral



Name:	Marta Penas-Prado	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Neuro Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2883 Contact us about clinical trials

General Information



Disease Group:	Brain CNS	Supported By:	N/A

Phase of Study:	Phase I	Return Visit:

Treatment Agents:	Mefloquine Memantine Metformin Temozolomide	Home Care:

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:

Description/
Intervention:

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.

Study Objectives / Outcomes

Primary Objective

To determine the safety and tolerability of temozolomide (TMZ) in combination with Metformin(MFRMN) and/or Mefloquine(MFLOQ) and/or Memantine(MEMTN) in patients receiving adjuvant therapy after completing external beam radiotherapy(XRT) in combination with chemotherapy for newly diagnosed glioblastoma multiforme(GBM).

Secondary Objective

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.

Study Status Information



Study Activation / Registration Date:	09/14/2011

IRB Review and Approval Date:	09/14/2011

Study Type:	Phase I

Recruitment Status:	Open

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) 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).

2) 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.

3) Patients must be >/= 18 years old.

4) Patients must have a Karnofsky performance status(KPS) of >/= 60.

5) Patients must have adequate bone marrow function (WBC >/= 3,000/�l, 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.

6) 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.

7) 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.

8) Patients must have completed standard radiation therapy with concurrent TMZ and must not have evidence of progressive disease on post treatment imaging.

9) Women of childbearing potential must have a negative serum or urine B-HCG pregnancy test documented within 72 hours of start of therapy.

10) Patients must be registered on the study within 5 weeks of completion of concurrent chemoradiation.

Exclusion Criteria:

1) 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.

2) 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.

3) 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.

4) Patients must not have active infection or serious intercurrent medical illness.

5) 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.

6) 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 durgs, 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.

7) 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.

Links

Registration Number: NCT01430351
Study Information on Clinical Trials Registry (clinicaltrials.gov)