Phase I Peposertib with Radiation and Temozolomide for Glioblastoma
This study is a Phase I trial testing a new drug called Peposertib. It's for people with newly diagnosed glioblastoma or gliosarcoma (types of brain cancer) where a specific biomarker (MGMT unmethylated) is present. Researchers want to find the safest dose of Peposertib when given with radiation therapy and temozolomide (a chemotherapy drug). They also want to see if Peposertib can cross the blood-brain barrier and how well this combination treatment works. Peposertib may help stop cancer cells from growing by blocking certain enzymes. Radiation therapy uses high-energy X-rays to kill cancer cells. The study aims to see if adding Peposertib to radiation therapy is more effective than radiation alone.
- Study design
- This is a Phase I interventional study with a planned enrollment of 29 participants. It is a dose-escalation study, meaning participants will receive increasing doses of Peposertib to find the safest and most effective amount.
- What's involved
- Participants will receive Peposertib by mouth and undergo radiation therapy. Some participants will also have surgical resection. The study will measure the maximum tolerated dose within the first 10 weeks and Peposertib levels in the blood at specific times on certain days.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoints are measured within the first 10 weeks of study treatment and at specific times after drug administration on fraction days 1 and 10.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04555577
Phase I Trial of DNA-PK Inhibitor (PEPOSERTIB ) in Combination With Radiation and Adjuvant Temozolomide in Newly Diagnosed MGMT Unmethylated and Recurrent Glioblastoma
Active, Not Recruiting
PHASE1Ages 18+InterventionalTreatmentM.D. Anderson Cancer CenterInvestigator-initiated
~29 participants
Updated 2026-07-30 on ClinicalTrials.gov
What's tested:PeposertibRadiation TherapyResectionTemozolomide
At a glance
Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Maximum tolerated dose (MTD) (Stage I)
Measured over Within the first 10 weeks of study treatment
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesTexas1
Study leadership
- Nazanin Majd, MD · PRINCIPAL_INVESTIGATOR · M.D. Anderson Cancer Center
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
Signed Informed Consent Form (ICF)
Be willing and able to provide written informed consent for the trial. Participants with cognitive impairment will be enrolled. Cognitive function will be assessed by the treating physician or designee through a neurological examination. The formal consent for such participants will be obtained from their legally authorized representative. For cognitively impaired adults who are enrolling in the study by consent of a legally authorized representative, assent of the subject is required for the subjects with the ability to communicate assent. This assent will be documented in subject fs consent note.
Age 18 years or older
Histologically confirmed World Health Organization (WHO) grade 4 glioma (GBM) or gliosarcoma, IDH wild-type, per WHO 2021 classification .IDH status is to be determined by IDH1 R132H immunohistochemistry except for patients ≤ age 54 in whom IDH sequencing will be required to detect non-canonical IDH mutations.
Have KPS of 3 60 or ECOG . 2 according to appendix 5.
A baseline MRI of brain obtained no more than 14 days prior to study enrollment on a stable or tapering dose of steroids for at least 3 days
Demonstrate adequate organ function as defined below.
All screening labs should be performed within 14 days prior to Day 1 of the study.
Female subjects of childbearing potential should have a negative serum pregnancy test within 14 days of Day 1 of the study.
Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile.
All screening labs should be performed within 14 days prior to Day 1 of the study.
Female subjects of childbearing potential should have a negative serum pregnancy test within 14 days of Day 1 of the study.
Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile.
Female subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
Male subjects should agree to use an adequate method of contraception during the course of the study.
Documentation of MGMT unmethylated GBM per testing at any Clinical Laboratory Improvement Amendment (CLIA) certified laboratory
Patients must have undergone brain surgery or biopsy and must not have had any further cancer treatments following surgery Recurrent GBM only
Any number of recurrences
Presence of enhancing, resectable disease
Candidate for re-radiation with ability to meet optic nerve and brainstem departmental dose constraints per treating physicians
6 mos or more since last radiation
Has not received re-radiation for GBM in the past except for stereotactic radiosurgery
Exclusion
Has received prior interstitial brachytherapy or implanted chemotherapy.
Active treatment with the tumor treating filed devices such as Optune during radiation will be excluded. Concurrent use of Optune during the adjuvant temozolomide cycles is allowed.
Any serious medical condition that interferes with adherence to study procedures.
Malignancies other than the disease under study within 2 years prior to Day 1 of the study, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score £ 6, and prostate-specific antigen \[PSA\] £ 10 mg/mL, etc).
Has known disease in the posterior fossa, gliomatosis cerebri, leptomeningeal disease, extracranial disease. Satellite lesions that are associated with a contiguous area of T2/FLAIR abnormality as the main lesion(s) and that are encompassed within the same radiotherapy port as the main lesion(s) are permitted.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating physician.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit.
Contraindication for undergoing MRIs.
Inability to comply with study and follow-up procedures.
Signs or symptoms of serious infection such as surgical wound infection, received IV antibiotics within 2 weeks prior to Day 1 of the study.
Administration of a live, attenuated vaccine within 4 weeks before Day 1 of the study or anticipation that such a live, attenuated vaccine will be required during the study
Influenza vaccination can be given. Patients must not receive live, attenuated influenza vaccine (e.g., FluMistâ) within 4 weeks prior to Day 1 of the study or at any time during the study and for 5 months after completion of adjuvant TMZ.
History of long QT syndrome.
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of PEPOSERTIB or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
Anticipation of need for a major surgical procedure during the course of the study (excluding patients in Stage II with planed non-urgent neuro-surgical resection)
Subjects at increased risk for radiation toxicities, such as known active collagen vascular disease (example; scleroderma, Sjogren's disease, etc) or other inherited radiation hypersensitivity syndromes (example; Gorlin syndrome, Fanconi anemia, ataxia-telangiectasia, etc.)
Active difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions (including pancreas deficiency requiring Creon therapy) that may hamper compliance and/or absorption of PEPOSERTIB.
Patients may not receive concomitant chemotherapy, immunotherapy, or radiotherapy (other than as pertained to GBM as described in section 1.1) while patients are on study.
History of MGMT methylated status performed at any CLIA certified laboratory. Recurrent GBM only
Prior history of scalp / surgical wound infection or wound dehiscence
Prior exposure to bevacizumab 6 weeks before enrollment.
Patients in Stage IIC and D (recurrent GBM) may receive bevacizumab during the adjuvant phase of treatment at the discretion of the treating physician, provided at least 6 weeks have elapsed since surgery and there are no wound healing concerns. A minimum washout period of 6-8 weeks is required from the last dose of prior bevacizumab before study enrollment.
No clinical drug-drug interaction (DDI) studies have been conducted with peposertib. Based on nonclinical data and basic static modeling using the proposed maximum therapeutic doses of 200 mg BID or 300 mg QD (tablet formulation), the following guidance applies: Subjects receiving or unable to discontinue foods, medications, or herbal supplements that are strong inducers or inhibitors of CYP3A4/5, CYP2C19, or CYP2C9 should be excluded from treatment with peposertib due to potential impact on drug exposure.
Substrates of CYP1A2, CYP2B6, CYP2C8, and CYP3A4/5 should be used with caution and monitored. Substrates with a narrow therapeutic index are prohibited during treatment with peposertib.
What this trial measures
- Maximum tolerated dose (MTD) (Stage I)Within the first 10 weeks of study treatment
Will employ the Bayesian optimal interval to find the MTD.
- Ability of Peposertib (M3814) to cross the blood brain barrier (Stage II)At 1, 2, and 4 hours after drug administration on fraction day 1 and at pre-dose and 1, 2, and 4 hours after drug administration on fraction day 10
Ability of the investigational drug to cross the blood brain barrier will be tested by measuring concentration of the drug within the blood and the resected brain tumor tissue. This will be correlated with biomarkers of deoxyribonucleic acid (DNA) damage in brain tumor tissue, blood, and hair follicle.