What side effects are associated with this type of intervention?

Common treatments for glioblastoma, such as enzyme inhibitors and radiation therapy, have several known side effects. Enzyme inhibitors like Peposertib can cause fatigue, nausea, diarrhea, and liver toxicity. Radiation therapy often results in fatigue, hair loss at the treatment site, skin changes, and potential long-term effects like cognitive decline and radiation necrosis. Combining these treatments may increase the risk of these side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Glioblastoma that involve enzyme inhibition and radiation therapy. Temozolomide, an oral chemotherapy drug that works by stopping tumor cells from dividing, is often used in combination with radiation therapy. This combination has been a standard treatment for newly diagnosed Glioblastoma. Additionally, other enzyme inhibitors and targeted therapies are being investigated in clinical trials to improve outcomes for patients with Glioblastoma.

What other types of research exist?

Promising novel alternatives for glioblastoma treatment include: 1) Tumor Treating Fields (TTFields) - a non-invasive therapy using electric fields to disrupt cancer cell division. 2) CAR T-cell therapy - a type of immunotherapy where a patient's T-cells are modified to target glioblastoma cells. 3) Oncolytic virus therapy - using genetically modified viruses to selectively infect and kill tumor cells. 4) Personalized vaccine therapy - vaccines created from a patient's own tumor cells to stimulate an immune response against the cancer.

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DNA Damage Response Inhibitor

Peposertib + Radiation + Temozolomide for Glioblastoma/Gliosarcoma

Phase 1

Recruiting

Led By Nazanin Majd

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

A baseline magnetic resonance imaging (MRI) of brain obtained no more than 14 days prior to study enrollment on a stable or tapering dose of steroids no greater than 4 mg a day of dexamethasone (or equivalent dose of other steroids) for at least 3 days

Documentation of MGMT unmethylated GBM per testing at any CLIA certified laboratory

Must not have

STAGE II: Patients who are s/p gross total resection with no remaining disease available for resection or tumor remaining in a region of the brain not amenable to resection

Subjects currently receiving or unable to stop using medications or herbal supplements known to be potent inhibitors or inducers of CYP 3A, CYP2C19, CYP2C9 and/or P-gp or drugs mainly metabolized by CYP3A, CYP2C19, CYP2C9 with a narrow therapeutic index

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing Peposertib combined with radiation therapy in patients with hard-to-treat brain tumors. Radiation kills the tumor cells, and Peposertib stops them from growing.

Who is the study for?

This trial is for adults with newly diagnosed MGMT unmethylated glioblastoma or gliosarcoma who have had surgery but no other treatments. They must be able to follow the study plan, have proper kidney and liver function, normal blood counts, and a stable condition on low-dose steroids. Women of childbearing age need a negative pregnancy test and agree to use birth control; men also need to use contraception.

What is being tested?

The trial tests Peposertib combined with radiation therapy followed by Temozolomide chemotherapy in patients with specific brain tumors. It aims to find the best dose of Peposertib that can be given safely and see if this combination works better than standard treatment alone.

What are the potential side effects?

Possible side effects include reactions related to Peposertib such as fatigue, nausea, skin changes from radiation, and typical chemotherapy-related issues like hair loss, lowered blood cell counts increasing infection risk, mouth sores, and constipation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I've had a brain MRI within the last 14 days and am on a low or reducing dose of steroids.

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My GBM is MGMT unmethylated according to a certified lab test.

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I am a woman who could still become pregnant.

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My kidney function is within the required range for the study.

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I am using two forms of birth control or am surgically sterile.

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My brain tumor is a grade IV glioma or gliosarcoma, IDH wild-type.

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I can care for myself and perform daily activities.

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I've had a brain MRI within the last 2 weeks and am on a low or reducing dose of steroids.

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I can care for myself but may not be able to do active work.

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My GBM is MGMT unmethylated according to a certified lab test.

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My brain tumor is a grade IV glioma or gliosarcoma, IDH wild-type.

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I've had brain surgery or a biopsy and no treatments after that.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I had surgery to remove a brain tumor and no visible tumor remains, or it's in a place that can't be surgically removed.

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I am not taking drugs that strongly affect certain liver enzymes or specific drug transporters.

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I have been treated with drugs that target cancer cell DNA repair mechanisms.

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I have a history of HIV infection.

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I have a history of long QT syndrome.

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I have issues swallowing or a gut condition that affects medication absorption.

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My cancer's MGMT status has been tested and is methylated.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Ability of Peposertib (M3814) to cross the blood brain barrier (Stage II)

Maximum tolerated dose (MTD) (Stage I)

Secondary study objectives

Dose-limiting toxicities (DLT) (Stage I)

Median overall survival (Stage II)

Median progression-free survival (Stage II)

Other study objectives

Alterations in tumor immune microenvironment

Pharmacodynamic properties of M3814

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Stage II (Peposertib, Radiation, Temozolomide, Surgery)Experimental Treatment4 Interventions

CONCURRENT: Patients receive Peposertib and undergo standard of care radiation therapy as in Stage I. Within 1-14 days after the completion of radiation therapy, patients undergo surgical resection. ADJUVANT: Patients receive temozolomide as in Stage I.

Group II: Stage I (Peposertib, Radiation therapy, Temozolomide)Experimental Treatment3 Interventions

CONCURRENT: Patients undergo standard of care radiation therapy daily (Monday-Friday) for 30 fractions. Patients also receive Peposertib PO on each day of radiation therapy and given 1-2 hours before each treatment fraction. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT: Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Peposertib

2021

Completed Phase 1

~20

Temozolomide

2010

Completed Phase 3

~1880

Resection

2020

Completed Phase 2

~1440

Radiation Therapy

2017

Completed Phase 3

~7250

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Glioblastoma treatments often involve a combination of enzyme inhibition and radiation therapy. Enzyme inhibitors, such as Peposertib, work by blocking specific enzymes that are essential for tumor cell growth and survival, thereby slowing down or stopping the proliferation of cancer cells. Radiation therapy uses high-energy x-rays to directly kill tumor cells by damaging their DNA, which prevents them from dividing and growing. These treatments are crucial for Glioblastoma patients because they target the aggressive nature of the tumor, aiming to control its growth and spread, ultimately improving patient outcomes and survival rates.