Drug Combination for Glioblastoma

Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: M.D. Anderson Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of chemotherapy drugs to determine the best dose and understand the side effects for treating glioblastoma multiforme, an aggressive brain cancer, after radiation therapy. The treatment uses several drugs together, such as temozolomide, memantine, metformin, and mefloquine, to assess their effectiveness in stopping or killing cancer cells. Different groups receive various combinations of these drugs to identify the most effective approach. The trial is suitable for individuals who have completed standard radiation therapy with temozolomide and show no signs of cancer progression on recent scans. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but if you are on enzyme-inducing anticonvulsants, you will need to stop them and wait for 2 weeks before starting the trial. Also, if you are on any of the study drugs already, you cannot join the trial for that specific drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have found temozolomide safe for patients over 65, helping them live longer when used after radiation therapy for glioblastoma, a type of brain cancer. In a study of 932 patients, a small number over 70 experienced serious blood-related side effects. While temozolomide works well, its safety for children remains unconfirmed.

Research indicates that adding metformin to temozolomide for glioblastoma treatment is generally safe and might extend patient survival compared to using temozolomide alone. Metformin is considered safe even for those without diabetes.

Memantine, often used for brain health, has been safely combined with temozolomide in past trials. Mefloquine, which increases cancer cells' sensitivity to treatment, has also proven safe when used with temozolomide and other drugs for glioblastoma.

Overall, these drug combinations are being tested to ensure safety and effectiveness. The goal is to find the best dose that patients can handle while maximizing treatment benefits.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for glioblastoma because they combine temozolomide, a standard chemotherapy drug, with other agents like memantine hydrochloride, metformin, and mefloquine. These combinations aim to enhance the effectiveness of temozolomide by targeting different pathways involved in tumor growth and resistance. For instance, metformin is primarily a diabetes drug but may help in reducing cancer cell energy production, while memantine is typically used for Alzheimer's and might protect brain function during treatment. Mefloquine, an anti-malarial, could potentially disrupt cancer cell membranes. By combining these agents, the treatments might overcome the limitations of current options, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

Research has shown that combining temozolomide with radiation therapy extends the lives of glioblastoma patients more than radiation alone. This trial tests different treatment combinations. Some participants will receive temozolomide with memantine and metformin, which studies suggest might improve survival rates. Others will receive temozolomide with mefloquine, as adding mefloquine could make cancer cells more responsive to treatment. Early trials indicated that these drugs can be safely combined and may increase the chances of destroying more tumor cells.16789

Who Is on the Research Team?

Vinay K. Puduvalli | MD Anderson Cancer ...

Vinay Puduvalli, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with glioblastoma or gliosarcoma who've finished radiation therapy. They must have a decent performance status, stable blood counts, normal liver and kidney function, and no progressive disease post-treatment. Women should not be pregnant and all participants must agree to use effective contraception.

Inclusion Criteria

I completed my chemoradiation treatment less than 5 weeks ago.
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
All patients must sign an informed consent indicating awareness of the investigational nature of the study and be registered prior to treatment with study drug
See 6 more

Exclusion Criteria

Patients with significant medical illnesses that cannot be adequately controlled with therapy or would compromise tolerance to treatment
I am currently being treated with a drug involved in the study.
My heart's electrical activity is normal, with no long QT interval or irregular rhythms.
See 5 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants complete external beam radiotherapy in combination with chemotherapy for newly diagnosed glioblastoma multiforme

6 weeks

Treatment

Participants receive temozolomide and a combination of memantine, mefloquine, and/or metformin as post-radiation adjuvant therapy

24 months
Courses repeat every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Ongoing every 3 months

What Are the Treatments Tested in This Trial?

Interventions

  • Mefloquine
  • Memantine Hydrochloride
  • Metformin Hydrochloride
  • Temozolomide
Trial Overview The study tests the safety and optimal doses of temozolomide combined with memantine hydrochloride, mefloquine, and metformin hydrochloride in treating brain tumors after radiation. It aims to see if this drug combo can make cancer cells more sensitive to treatment.
How Is the Trial Designed?
8Treatment groups
Experimental Treatment
Group I: Arm 8 (TMZ, memantine hydrochloride, metformin, mefloquine)Experimental Treatment4 Interventions
Group II: Arm 7 (temozolomide, mefloquine, metformin hydrochloride)Experimental Treatment3 Interventions
Group III: Arm 6 (temozolomide, memantine hydrochloride, metformin)Experimental Treatment3 Interventions
Group IV: Arm 5 (temozolomide, memantine hydrochloride, mefloquine)Experimental Treatment3 Interventions
Group V: Arm 4 (temozolomide, metformin hydrochloride)Experimental Treatment2 Interventions
Group VI: Arm 3 (temozolomide, mefloquine)Experimental Treatment2 Interventions
Group VII: Arm 2 (temozolomide, memantine hydrochloride)Experimental Treatment2 Interventions
Group VIII: Arm 1 (temozolomide)Experimental Treatment1 Intervention

Temozolomide is already approved in European Union, United States for the following indications:

🇪🇺
Approved in European Union as Temodal for:
🇺🇸
Approved in United States as Temodar for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Citations

A rapid and systematic review of the effectiveness of ...The key results were that temozolomide may increase progression-free survival but has no significant impact on overall length of survival. The main effect from ...
Clinical trial finds that adding the chemotherapy pill ...“We found that the 10-year survival rate was 70% with the combined treatment with temozolomide chemotherapy and radiation, compared to 47% with ...
The role of temozolomide as adjuvant therapy in glioblastoma ...TMZ has been shown to significantly improve patient outcomes, notably increasing the median overall survival compared to RT alone [2]. This ...
Temozolomide (TMZ) in the Treatment of Glioblastoma ...The purpose of this paper is to describe the place of this anticancer drug and its efficacy in GBM therapy based on recent clinical trials.
Temozolomide based treatment in glioblastoma: 6 vs. 12 ...The present data suggested that extended adjuvant temozolomide appeared to be more effective than the conventional six cycles.
TEMODAR (temozolomide) Label - accessdata.fda.govIn the entire safety database for which hematologic data exist (N=932), 7% (4/61) and 9.5% (6/63) of patients over age 70 experienced Grade 4 neutropenia or ...
temodar_pi.pdfSafety and effectiveness of TEMODAR capsules were assessed, but not established, in 2 open-label studies in pediatric patients aged 3 to 18 years. In one study, ...
Study Details | NCT01107522 | Safety and Tolerability of ...The purpose of this study is to determine the safety, tolerability, and the maximum tolerated dose/recommended phase II dose of carboxyamidotriazole orotate ...
Temozolomide (oral route) - Side effects & dosageTemozolomide is used to treat specific types of brain cancer (eg, glioblastoma ... Safety and efficacy have not been established. .
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