Peposertib and Radiation Therapy, Followed by Temozolomide for the Treatment of Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma or Gliosarcoma

NCT04555577 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2019-1035NCI-2020-04491
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial investigates the side effects and best dose of Peposertib, and to see how well it works in combination with radiation therapy in treating patients with newly diagnosed MGMT unmethylated glioblastoma or gliosarcoma. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Peposertib may further stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Peposertib with radiation therapy may work better than radiation therapy alone in treating patients with glioblastoma or gliosarcoma.

Conditions

Glioblastoma; Gliosarcoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) (Stage I)

  Will employ the Bayesian optimal interval to find the MTD.

  Within the first 10 weeks of study treatment

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

  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.

  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

Secondary Outcomes (7)

• Dose-limiting toxicities (DLT) (Stage I)

  Within the first 10 weeks of study treatment

• Overall response rate (Stage I)

  Up to 3 years

• Median progression-free survival (Stage I)

  From study enrollment until time of first occurrence of disease progression, relapse, or death due to disease, assessed up to 3 years

• Median overall survival (Stage I)

  Up to 3 years

• Overall response rate (Stage II)

  Up to 3 years

Other Outcomes (2)

• Pharmacodynamic properties of M3814

  Up to 3 years

• Alterations in tumor immune microenvironment

  Up to 3 years

Study Arms (2)

Stage I (Peposertib, Radiation therapy, Temozolomide)

EXPERIMENTAL

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.

Drug: Peposertib; Radiation: Radiation Therapy; Drug: Temozolomide

Stage II (Peposertib, Radiation, Temozolomide, Surgery)

EXPERIMENTAL

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.

Drug: Peposertib; Radiation: Radiation Therapy; Procedure: Resection; Drug: Temozolomide

Interventions

Peposertib DRUG

Given PO

Stage I (Peposertib, Radiation therapy, Temozolomide); Stage II (Peposertib, Radiation, Temozolomide, Surgery)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Stage I (Peposertib, Radiation therapy, Temozolomide); Stage II (Peposertib, Radiation, Temozolomide, Surgery)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Stage II (Peposertib, Radiation, Temozolomide, Surgery)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ

Stage I (Peposertib, Radiation therapy, Temozolomide); Stage II (Peposertib, Radiation, Temozolomide, Surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• oPatients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
• oPatients receiving oral antibiotics for minor infections such as urinary tract infection are eligible.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

peposertib; Radiotherapy; Radiation; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nazanin Majd, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nazanin Majd, MD

CONTACT

713-792-2883; nkmajd@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2020
• First Posted: September 18, 2020
• Study Start: September 20, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: October 29, 2025

Record last verified: 2025-10

Locations

US (1)