GlioblastomaPhase 1NCT05917145
ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Treatment of Recurrent High-Grade Glioma
A Phase 1 study testing WSD0628 in people with Glioblastoma, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is to test WSD0628 in combination with radiation therapy for recurrent brain tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- WSD0628
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jan 2024to 31 May 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu
Willilam G. Breen, MD
About this study
Official title: MC220712 Phase 0/I Clinical Trial of the ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Recurrent High-Grade Glioma
The purpose of this study is to test WSD0628 in combination with radiation therapy for recurrent brain tumors.
Read the detailed description
High grade gliomas are the most common primary brain tumor in adults. Despite aggressive treatment including surgery, chemotherapy, and radiation, these tumors have a dismal prognosis. Following a radiation therapy, almost 80% of them recur locally. The focus of this project is the development of a radiation sensitizer (a small molecule ATM inhibitor, WSD0628) with the goal to enhance the efficacy of radiation therapy. The first step will be to establish a pre-clinical PK→PD→efficacy model to describe WSD0628 plasma and tumor concentrations associated with robust ATM inhibition and radiosensitizing effects. This model will be instrumental in interpreting the pharmacokinetic (PK) data and dosage selection in the proposed first-in-human, Phase 1, open-label, multicenter, single-arm, dose-escalation, and dose-expansion study in approximately 42 adult patients with recurrent high-grade glioma. The aims of the study are to assess the safety, tolerability, PKs and preliminary anti-tumor activity of WSD0628 in combination with radiation therapy. The dose-escalation portion of the study (Part A) will enroll approximately 24 patients and is comprised of Bayesian Optimal Interval (BOIN) design with target toxicity rate of 22%-33%. Once the recommended Phase 2 dose (RP2D) is established, Part B of the study will commence in which an additional 12 patients will be enrolled and treated at the RP2D for further evaluation of safety and efficacy (standard expansion cohort), and an additional 6 patients will have a tissue evaluation of tumor penetrance after a one-time dose of study drug prior to radiosurgery and surgical resection (Phase 0, tumor penetrance cohort). Tumor response will be assessed, using brain magnetic resonance imaging (MRI) with assessment based on the Response Assessment in Neuro-Oncology (RANO) criteria, and safety will include analysis of adverse events (AEs) and laboratory data. Additionally, PK, pharmacodynamic (PD), overall survival, progression-free survival, overall response rate, and patient-reported outcomes will be evaluated. The maximum duration of Part A will be 32 months and Part B,12 months. Funding Source - FDA OOPD
- Conditions
- Glioblastoma
- Being tested
- WSD0628
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WSD0628Drug
A non-toxic compound and inhibits the DNA damage response associated with radiation therapy. • WSD-0628 radio sensitizes Glioblastoma cells.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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 Receives: Drug: WSD0628 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
All AEs must be documented in the subject's medical record
Measured: 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)
Overall response rate defined as the proportion of patients who achieve a partial response (PR) or a complete response (CR) divided by the total number of patients who received therapy. Exact binomial 95% confidence intervals for the overall response rate will be calculated.
Measured: 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)
The primary measure of response will be by serial measures of the product of the two largest cross-sectional diameters (bidirectional product) using the RANO and iRANO criteria.
Measured: 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
measured by MRI/CT scan evaluations
Measured: Beginning of study therapy until the first occurrence of progression or death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2023
- Study start17 Jan 2024
- Primary completion31 May 2028 (estimated)
- Study completion31 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Group A - Dose Escalation Phase Group B - Dose Expansion Group C - Tumor Penetrance Cohort
- Masking
- None (open label)
- Enrolment
- 94 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- William G. Breen, MD, Principal investigator, Mayo ClinicJann N. Sarkaria, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05917145
- Sponsor's protocol ID
- MC220712
- Other IDs
- R01FD007842, 23-004794
- Status last verified
- Apr 2026
- First submitted
- 15 Jun 2023
- Last updated
- 21 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MC220712 Phase 0/I Clinical Trial of the ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Recurrent High-Grade Glioma
- ClinicalTrials.gov ID
- NCT05917145
- Acronym / sponsor ID
- MC220712
- Conditions
- Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 94 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 17 Jan 2024 (actual)
- Primary completion
- 31 May 2028 (estimated)
- Study completion
- 31 May 2029 (estimated)
- First posted
- 23 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test WSD0628 in combination with radiation therapy for recurrent brain tumors.
Detailed description
High grade gliomas are the most common primary brain tumor in adults. Despite aggressive treatment including surgery, chemotherapy, and radiation, these tumors have a dismal prognosis. Following a radiation therapy, almost 80% of them recur locally. The focus of this project is the development of a radiation sensitizer (a small molecule ATM inhibitor, WSD0628) with the goal to enhance the efficacy of radiation therapy. The first step will be to establish a pre-clinical PK→PD→efficacy model to describe WSD0628 plasma and tumor concentrations associated with robust ATM inhibition and radiosensitizing effects. This model will be instrumental in interpreting the pharmacokinetic (PK) data and dosage selection in the proposed first-in-human, Phase 1, open-label, multicenter, single-arm, dose-escalation, and dose-expansion study in approximately 42 adult patients with recurrent high-grade glioma. The aims of the study are to assess the safety, tolerability, PKs and preliminary anti-tumor activity of WSD0628 in combination with radiation therapy. The dose-escalation portion of the study (Part A) will enroll approximately 24 patients and is comprised of Bayesian Optimal Interval (BOIN) design with target toxicity rate of 22%-33%. Once the recommended Phase 2 dose (RP2D) is established, Part B of the study will commence in which an additional 12 patients will be enrolled and treated at the RP2D for further evaluation of safety and efficacy (standard expansion cohort), and an additional 6 patients will have a tissue evaluation of tumor penetrance after a one-time dose of study drug prior to radiosurgery and surgical resection (Phase 0, tumor penetrance cohort). Tumor response will be assessed, using brain magnetic resonance imaging (MRI) with assessment based on the Response Assessment in Neuro-Oncology (RANO) criteria, and safety will include analysis of adverse events (AEs) and laboratory data. Additionally, PK, pharmacodynamic (PD), overall survival, progression-free survival, overall response rate, and patient-reported outcomes will be evaluated. The maximum duration of Part A will be 32 months and Part B,12 months. Funding Source - FDA OOPD
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Group A - Dose Escalation Phase Group B - Dose Expansion Group C - Tumor Penetrance Cohort
| Arm | Type | Receives |
|---|---|---|
| Group A (Dose Escalation) | Experimental | Drug: WSD0628WSD0628 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. |
| Group B (Dose Expansion) | Experimental | Drug: WSD0628WSD0628 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. |
| Group C (Tumor Penetrance Treatments) | Experimental | Drug: WSD0628One 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Age ≥ 18 years
- Histological confirmation of one of the following:
- 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)
Key exclusion criteria (29 listed)
- 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:
- Uncontrolled intercurrent illness including, but not limited to:
- Any of the following cardiac criteria:
- Known coagulopathy increasing the risk of bleeding or history of clinically significant hemorrhage, including significant intracranial tumor related hemorrhage
- Any of the following medications:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WSD0628A non-toxic compound and inhibits the DNA damage response associated with radiation therapy. • WSD-0628 radio sensitizes Glioblastoma cells. | Drug | Group A (Dose Escalation), Group B (Dose Expansion), Group C (Tumor Penetrance Treatments) |
Primary outcome
Determine the maximum tolerated dose of WSD0628 in combination with radiation therapy for patients with recurrent high-grade glioma.
Time frame: 4 weeks after last day of RT (up to 60 days)
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.
Determine the recommended phase 2 dose of WSD0628 in combination with radiation therapy for patients with recurrent high-grade glioma.
Time frame: 4 weeks after last day of RT (up to 60 days)
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 secondary outcomes
Measure the incidence of acute adverse effects related to WSD0628 delivered concurrently with radiation
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: Beginning of study therapy until the first occurrence of progression or death
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
William G. Breen, MD principal investigator
Mayo Clinic
Jann N. Sarkaria, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing WSD0628 in people with Glioblastoma, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials Referral Office (855-776-0015, mayocliniccancerstudies@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the maximum tolerated dose of WSD0628 in combination with radiation therapy for patients with recurrent high-grade glioma. (time frame: 4 weeks after last day of RT (up to 60 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2026.