ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Treatment of Recurrent High-Grade Glioma

NCT05917145 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: MC220712R01FD00784223-004794
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test WSD0628 in combination with radiation therapy for recurrent brain tumors.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Determine the maximum tolerated dose of WSD0628 in combination with radiation therapy for patients with recurrent high-grade glioma.

  Use Bayesian Optimal Interval (BOIN) design to inform dose escalation and de-escalation decisions and to ultimately determine the maximum tolerated dose level (MTD) of WSD0628 in patient population.

  4 weeks after last day of RT (up to 60 days)

• Determine the recommended phase 2 dose of WSD0628 in combination with radiation therapy for patients with recurrent high-grade glioma.

  Evaluate biologic activity measures using rank-based desirability scores (RDS) generated for each of the dose levels to identify which of these scores best when looking jointly at toxicity and biologic activity. The rank-based desirability scores (RDS) for this BOIN12 design will be used to help identify the best dose

  4 weeks after last day of RT (up to 60 days)

Secondary Outcomes (4)

• Measure the incidence of acute adverse effects related to WSD0628 delivered concurrently with radiation

  4 weeks after last day of RT (up to 60 days)

• Assess anti-tumor activity of WSD0628 delivered concurrently with radiation, including intracranial overall response rate (ORR)

  4 weeks after last day of RT (up to 60 days)

• Assess anti-tumor activity of WSD0628 delivered concurrently with radiation, including progression-free survival (PFS)

  Beginning of study therapy until the first occurrence of progression or death

• Assess anti-tumor activity of WSD0628 delivered concurrently with radiation, including volumetric change in tumor size

  Beginning of study therapy until the first occurrence of progression or death

Study Arms (3)

Group A (Dose Escalation)

EXPERIMENTAL

WSD0628 treatment should be started the day before radiation therapy starts (Day 1). Radiation therapy is given for 10 consecutive business days (Day 2-15, not including weekends and holidays), and WSD0628 will only be given on those 10 consecutive business days ≥30 minutes but ≤2 hours before radiation.

Drug: WSD0628

Group B (Dose Expansion)

EXPERIMENTAL

WSD0628 treatment should be started the day before radiation therapy starts (Day 1). Radiation therapy is given for 10 consecutive business days (Day 2-15, not including weekends and holidays), and WSD0628 will only be given on those 10 consecutive business days ≥30 minutes but ≤2 hours before radiation. The Group B (Dose Expansion) portion of the study will be opened after the Group A (Dose Escalation) is complete.

Drug: WSD0628

Group C (Tumor Penetrance Treatments)

EXPERIMENTAL

One treatment of WSD0628 will be given prior to radiation and surgical resection will be performed on the same day. The two doses given will be determined by Group A and Group B. Patients will be randomized in a 1:1 fashion. * Dose level 1: minimally radiosensitizing concentration of WSD0628 will be achieved. * Dose level 2: selected based on a prediction that a maximally radiosensitizing concentration of WSD0628 will be achieved. This portion of the study will open after Group A (Dose Escalation) is complete. This portion of the study will open to patients with recurrent high-grade glioma to further evaluate the efficacy, safety, tolerability, pharmacokinetics and biological activity of WSD0628 when combined with radiation therapy in specific patient subgroups

Drug: WSD0628

Interventions

WSD0628 DRUG

A non-toxic compound and inhibits the DNA damage response associated with radiation therapy. • WSD-0628 radio sensitizes Glioblastoma cells.

Group A (Dose Escalation); Group B (Dose Expansion); Group C (Tumor Penetrance Treatments)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Histological confirmation of one of the following:
• Glioblastoma, IDH-wildtype
• Grade 3 or 4 IDH1/2 mutant astrocytoma (2021 WHO classification)
• Measurable disease as defined in Section 11.0
• Disease progression after previous treatment for glioma with radiation and chemotherapy
• Minimum life expectancy of at least 3 months
• Group C only: Dose Expansion, Brain Tumor Penetration Group: plan for radiosurgery and surgical resection as part of routine clinical care
• ECOG Performance Status (PS) 0, 1 or 2 (Appendix I)
• The following laboratory values obtained ≤15 days prior to registration:
• Hemoglobin ≥9.0 g/dL
• Leukocytes ≥3.0 x 109/L
• Absolute neutrophil count (ANC) ≥1500/mm3 or 1.5 x 109/L
• Platelet count ≥100,000/mm3 or 100 x 109/L
• Total bilirubin ≤1.5 x ULN and \<3 mg/dL for patients with Gilbert's disease

You may not qualify if:

• Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
• Uncontrolled intercurrent illness including, but not limited to:
• ongoing or active infection
• symptomatic congestive heart failure
• unstable angina pectoris
• cardiac arrhythmia
• or psychiatric illness/social situations that would limit compliance with study requirements
• Any of the following cardiac criteria:
• Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>480 milliseconds (ms) (CTCAE Grade 1) using Fredericia's QT correction formula.
• History of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT. Syndrome).
• Use of concomitant medications that prolong the QT/QTc interval
• History of myocardial infarction ≤6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Glioblastoma

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

Study Officials

• William G. Breen, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Jann N. Sarkaria, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

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

Model Details: Group A - Dose Escalation Phase Group B - Dose Expansion Group C - Tumor Penetrance Cohort

Study Record Dates

• First Submitted: June 15, 2023
• First Posted: June 23, 2023
• Study Start: January 17, 2024
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2029
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)