Testing WSD0628 with radiation for recurrent brain tumors
MC220712 Phase 0/I Clinical Trial of the ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Recurrent High-Grade Glioma
This study is testing a new drug called WSD0628 combined with radiation to see if it can help adults with recurrent brain tumors like glioblastoma feel better and improve their treatment outcomes.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 94 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Mayo Clinic Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, radiation |
| Locations | 1 site (Rochester, Minnesota) |
| Trial ID | NCT05917145 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the safety and effectiveness of WSD0628, a small molecule ATM inhibitor, in combination with radiation therapy for patients with recurrent high-grade gliomas, including glioblastoma. The study will follow a dose-escalation design, enrolling approximately 42 adult patients to assess pharmacokinetics, tolerability, and preliminary anti-tumor activity. The first part of the trial will focus on determining the recommended Phase 2 dose, while the second part will further evaluate safety and efficacy at this established dose. The goal is to enhance the efficacy of radiation therapy for these challenging tumors.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with recurrent high-grade gliomas who have experienced disease progression after prior treatments.
Not a fit: Patients with low-grade gliomas or those who have not previously undergone radiation and chemotherapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly improve outcomes for patients with recurrent glioblastoma by enhancing the effectiveness of radiation therapy.
How similar studies have performed: While the specific combination of WSD0628 and radiation is novel, similar approaches using radiation sensitizers have shown promise in other studies.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 * Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 x ULN * PT/INR/aPTT ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy * Calculated creatinine clearance ≥45 ml/min using the Cockcroft-Gault formula below: * Creatinine clearance for males = (140-age)(weight in kg)(72)(serum creatinine inmgdL⁄) * Creatinine clearance for females = (140-age)(weight in kg)(0.85)(72)(serum creatinine inmgdL⁄) * Negative pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only * Willing to take light-protective measures during the study and for two weeks after their last dose of WSD0628 * Provide written informed consent * Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) * Willingness to provide mandatory tissue specimens for correlative research Exclusion Criteria: * 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 * Known coagulopathy increasing the risk of bleeding or history of clinically significant hemorrhage, including significant intracranial tumor related hemorrhage * Any of the following medications: * Enzyme-inducing anticonvulsants within two weeks of enrollment NOTE: Patients can be enrolled after a change to non-enzyme inducing anticonvulsants) * Patients taking more than 8 mg of dexamethasone per day (or equivalent steroid dose) at time of enrollment * Any of the following prior therapies: * Radiation therapy \<= 26 weeks prior to registration (including gamma tiles) * Chemotherapy, immunotherapy, or any investigational drug \<= four weeks prior to registration, * or carmustine (BCNU) or lomustine (CCNU) \<= six weeks prior to registration * Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease * History of hypersensitivity to active or inactive excipients of WSD0628 or drugs with a similar chemical structure or class to WSD0628 * Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0628 * Uncontrolled hypertension * History of severe brain-injury or stroke * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
Where this trial is running
Rochester, Minnesota
- Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)
Study contacts
- Principal investigator: William G. Breen, MD — Mayo Clinic
- Study coordinator: Clinical Trials Referral Office
- Email: mayocliniccancerstudies@mayo.edu
- Phone: 855-776-0015
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.