A Phase 3 GBM Trial for MGMT Unmethylated Patients

Clinical TrialsPosted: March 9, 2026 • By: PACT

When you or someone you love is newly diagnosed with glioblastoma, one of the first pieces of information you'll hear is a biomarker result: MGMT methylated or unmethylated. For families dealing with an unmethylated result, that news often comes with a difficult follow-up — that the standard chemotherapy, temozolomide, may work less well for their tumor. That's a hard thing to absorb in an already overwhelming moment.

A Phase 3 clinical trial called Gliofocus is now actively enrolling patients in exactly that situation. It's one of the largest glioblastoma trials currently recruiting in the US, and it's specifically designed for people with newly diagnosed, MGMT unmethylated GBM — a group that has historically had fewer tailored options.

Here's what the trial actually involves, who qualifies, and how to find out if it might be worth exploring with your care team.

What Is the Gliofocus Trial?

The Gliofocus study (NCT06388733) is a global, open-label, randomized Phase 3 trial. Phase 3 means this is the final stage of clinical testing before a treatment can be considered for FDA approval — it compares a new approach directly against the current standard of care in a large group of patients.

The trial is sponsored by the Ivy Brain Tumor Center and led by Study Chair Nader Sanai, MD. According to ClinicalTrials.gov (NCT06388733), the trial is comparing niraparib to temozolomide (TMZ) — the chemotherapy currently used as standard of care — in adults who have just been diagnosed with MGMT unmethylated glioblastoma.

The trial's primary question, as listed on ClinicalTrials.gov: Does niraparib improve overall survival compared to TMZ? The primary outcome is measured at 24 months.

A total of 450 participants will be enrolled across 93 participating locations worldwide, according to ClinicalTrials.gov.

What Is MGMT Unmethylated GBM — and Why Does It Matter Here?

Your tumor's MGMT status is determined by a lab test on the tissue removed during surgery. MGMT refers to a DNA-repair gene. When that gene is "methylated," it's essentially switched off — and that makes the tumor more vulnerable to temozolomide, which works by damaging DNA.

When the gene is "unmethylated," the repair system stays active. The tumor can fix the damage that TMZ causes, making the chemotherapy less effective.

Patients with MGMT unmethylated GBM are a significant portion of newly diagnosed GBM cases, and the Gliofocus trial was designed specifically because this population has an unmet need for better treatment options.

Who May Be Eligible for the Gliofocus Trial?

Based on eligibility criteria listed on ClinicalTrials.gov (NCT06388733), participants generally need to meet the following criteria. This is not a complete list — your care team would need to review the full protocol.

You may be eligible if you:

Are 18 years or older
Have a newly diagnosed glioblastoma confirmed by tissue biopsy or resection, per 2021 WHO classification guidelines
Have MGMT unmethylated status, confirmed locally by a validated assay (PSQ or qMS-PCR)
Have received no prior treatment for GBM other than surgery (resection or biopsy)
Are considered suitable for standard radiation therapy (60 Gy in 30 fractions)
Have enough tissue available for central pathology review

You may not be eligible if you:

Have had prior GBM treatment, including brachytherapy or BCNU wafers placed during surgery
Are pregnant, planning to become pregnant, or breastfeeding without meeting specific contraception requirements

These are the key criteria listed on ClinicalTrials.gov. Other criteria apply. Please review the full list at clinicaltrials.gov/study/NCT06388733 and discuss with your oncologist.

What Would Participating Actually Look Like?

If you're randomized into the trial, you'd be assigned to one of two treatment arms: niraparib or temozolomide. Both are taken alongside standard radiation therapy — you would not be giving up radiation as part of your treatment plan.

The trial is open-label, which means both you and your care team know which treatment you're receiving. There is no placebo arm.

Because this is a Phase 3 trial enrolling 450 people across 93 sites, many patients may not have to travel far. The trial is recruiting across a wide range of US institutions, including:

Ivy Brain Tumor Center, Phoenix, AZ
University of Alabama at Birmingham, Birmingham, AL
Moores UCSD Cancer Center and Scripps Cancer Center, La Jolla, CA
Indiana University, Indianapolis, IN
Tufts Medical Center, Boston, MA
University of Michigan Rogel Cancer Center, Ann Arbor, MI
Allina Health, Minneapolis, MN
The NeuroMedical Center, Baton Rouge, LA
MaineHealth Maine Medical Center Care, South Portland, ME

(This is a partial list. See ClinicalTrials.gov for all enrolling sites.)

What This Means for Patients

For families who've just received an MGMT unmethylated result, the Gliofocus trial represents a concrete, actionable next step to ask about — right now, while enrollment is open.

The timing matters. Gliofocus specifically requires that patients have had no prior GBM treatment beyond surgery. That means enrollment conversations need to happen early in the treatment planning process, ideally before chemotherapy begins. For families dealing with a new diagnosis, the window for trial enrollment can feel impossibly small — knowing this trial exists, and that it has nearly 100 sites, puts that conversation within reach.

A few things worth knowing as you think this through:

This is research. Clinical trials are designed to find out whether a treatment works better — not to guarantee a specific outcome. Outcomes cannot be predicted.
You have a choice. Participation is voluntary. You can ask about it, discuss it with your team, and decide without pressure.
Getting a second opinion is reasonable. If your current oncologist isn't affiliated with a trial site, a second opinion at a participating institution is a legitimate path.

How to Find Out More

Talk to your neuro-oncologist or oncology team. Share the trial name (Gliofocus) and the NCT number: NCT06388733. Ask whether your tumor's MGMT status has been confirmed and whether you'd meet the basic eligibility criteria.
Review the trial directly. The full eligibility criteria, site list, and protocol details are at clinicaltrials.gov/study/NCT06388733.
Use PACT to find your options. PACT AI matches patients to actively enrolling brain cancer trials based on your specific diagnosis, biomarkers, prior treatments, and location — at no cost. Visit pact-ai.com to get started.

Frequently Asked Questions

Do I need to have the MGMT test before I can explore this trial?

Yes — according to ClinicalTrials.gov (NCT06388733), MGMT unmethylated status confirmed by a validated local assay is a required inclusion criterion. If your team hasn't ordered this test yet, that's the first step to ask about.

Can I enroll if I already started temozolomide?

No. The trial requires that participants have received no prior treatment for GBM other than surgical resection or biopsy. If you've already begun chemotherapy, you would not be eligible based on the criteria listed on ClinicalTrials.gov.

Is there a placebo in this trial?

No. Both arms of the trial receive an active treatment — either niraparib or temozolomide — and the trial is open-label, so you would know which one you are receiving.

How many locations are enrolling in the US?

According to ClinicalTrials.gov (NCT06388733), the trial has 93 participating locations. Many are in the United States. The full site list is available at the ClinicalTrials.gov entry for the trial.

This post is for informational purposes only and does not constitute medical advice.