WP1066 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma

NCT05879250 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NU 21C06NCI-2022-09279STU00216108P30CA060553
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests how well the combination of WP1066 and radiation therapy works in treating newly diagnosed glioblastoma. Glioblastoma is difficult to treat effectively because the cells within the tumor vary widely and are controlled by factors within and around the tumor, requiring multiple approaches to treat the tumor. The study drug WP1066 targets a specific pathway, known as STAT3, which is responsible for promoting tumor growth and causing the body's immune system to avoid attacking the tumor. Radiation therapy prevents glioblastoma from growing. Giving WP1066 with radiation therapy may prevent glioblastoma from growing and prolong survival.

Conditions

Glioblastoma, IDH-Wildtype; MGMT-Unmethylated Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) (Cohort 1)

  For PFS analysis, disease progression is defined as progressive disease (PD) per Response Assessment in Neuro-Oncology (RANO) criteria Will be summarized using the Kaplan-Meier method.

  From subject registration to the earlier of the day of first documented disease progression or death from any cause, assessed up to 36 months post-registration

• Tumor microenvironment activation and cluster interactions (Cohort 2)

  Up to 36 months post-registration

Secondary Outcomes (5)

• Overall Survival (OS)

  From the date of initial diagnosis until death from any cause, assessed up to 36 months

• Overall Response Rate (ORR)

  Up to 36 months post-registration

• Duration of response (DOR)

  Up to 36 months post-registration

• Frequency of adverse events

  Up to 36 months post-registration

• Time to response/progression

  Up to 36 months post-registration

Study Arms (2)

Cohort I (WP1066, radiation)

EXPERIMENTAL

Patients whose tumor was completely removed at the time of initial surgery receive WP1066 PO for 6 weeks during routine radiation therapy, and then for twelve 28-day cycles on study. Patients also undergo MRI and collection of blood samples throughout the trial.

Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Radiation: Radiation Therapy; Drug: STAT3 Inhibitor WP1066

Cohort II (WP1066, radiation, surgery)

EXPERIMENTAL

Patients whose tumor was not fully removed at the time of initial surgery receive WP1066 PO for 6 weeks during routine radiation therapy on study. Patients may then undergo possible surgery or open biopsy if eligible, followed by twelve 28-day cycles of WP1066 PO on study. Patients also undergo MRI and collection of blood samples throughout the trial.

Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Radiation: Radiation Therapy; Drug: STAT3 Inhibitor WP1066; Procedure: Surgical Procedure

Interventions

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Cohort I (WP1066, radiation); Cohort II (WP1066, radiation, surgery)

Radiation Therapy RADIATION

Undergo routine radiation therapy

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

Cohort I (WP1066, radiation); Cohort II (WP1066, radiation, surgery)

STAT3 Inhibitor WP1066 DRUG

Given PO

Also known as: WP 1066, WP-1066, WP1066

Cohort I (WP1066, radiation); Cohort II (WP1066, radiation, surgery)

Surgical Procedure PROCEDURE

Undergo removal or biopsy of tumor

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Cohort II (WP1066, radiation, surgery)

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Cohort I (WP1066, radiation); Cohort II (WP1066, radiation, surgery)

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed, histologically confirmed World Health Organization (WHO) glioblastoma multiforme (GBM), IDH wild-type
• External pathology reports are permitted for confirmation of histological diagnosis
• Documentation of isocitrate dehydrogenase (IDH) wild-type status will be by IDH1 R123H immunohistochemistry, except for patients =\< age 54 for whom IDH sequencing will be required to detect noncanonical IDH mutations
• Documentation of O6-methylguanine-DNA methyltransferase (MGMT) unmethylated status per testing at any Clinical Laboratory Improvement Amendment (CLIA) certified laboratory
• Cohort 1 only: Patients with prior gross total resection (GTR)
• Cohort 2 only: Patients without prior gross total resection (GTR)
• Cohort 2 only: Measurable disease in the brain (per RANO criteria) on brain magnetic resonance imaging (MRI) scan conducted within =\< 4 weeks prior to initiating trial therapy
• Cohort 2 only: Patients who would benefit from non-emergent, palliative surgical resection, in the opinion of the local site's tumor board
• Able to initiate trial therapy within 8 weeks of the initial brain surgical procedure (biopsy or resection) that lead to the patient's initial diagnosis of GBM
• Age \>=18 years
• Karnofsky performance scale score \>= 60%
• White blood cell (WBC) count \>= 3.0 x 10\^9/L (within =\< 30 days prior to registration) (without growth factor support and/or receipt of blood products within =\< 14 days prior to testing)
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L (within =\< 30 days prior to registration) (without growth factor support and/or receipt of blood products within =\< 14 days prior to testing)
• Platelet count \>= 75 x 10\^9/L (within =\< 30 days prior to registration) (without growth factor support and/or receipt of blood products within =\< 14 days prior to testing)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) or direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN (within =\< 30 days prior to registration)

You may not qualify if:

• Receipt of investigational agents within =\< 2 weeks prior to registration
• Prior receipt of gene therapy, at any time
• Prior receipt of bevacizumab, at any time
• Prior receipt of Gliadel, at any time
• Patients who are on active therapy with Optune and who are unable to safely discontinue Optune prior to initiating trial therapy Note: Patients who can safely discontinue Optune prior to initiating trial therapy may participate
• Patients who are on active therapeutic anti-cancer therapy and who are unable to discontinue the anti-cancer therapy prior to initiating trial therapy Note: Patients who discontinue anti-cancer therapy prior to initiating trial therapy may participate. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen for this trial may participate
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to WP1066 or its excipients
• Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy Note: These patients are ineligible because of the potential for pharmacokinetic interactions with WP1066. (HIV testing is not required, unless mandated by a local health authority.)
• Patients who have received drugs that significantly interact with CYP450 enzyme(s) within =\< 2 weeks prior to planned first study treatment day Note: Patients who are able to safely discontinue the aforementioned agents \> 2 weeks prior to initiating treatment with WP1066 may participate. The enzymatic metabolism profile of WP1066 is unknown. Drugs that have a minor interaction with CYP450 are allowed, and drugs with a moderate interaction are allowed at the principal investigators (PI's) discretion. Zofran (ondansetron) is allowed
• Patients who have received any of the following agents within 7 days of planned first study treatment day:
• Agents that are predominantly CYP2D6, 2C9, or 2C19 substrates
• Agents that are strong inhibitors or inducers of CYP2D6, 2C9, or 2C19
• Agents that are sensitive substrates of CYP3A4 with narrow therapeutic range Note: Patients who are able to safely discontinue the aforementioned agents \> 7 days prior to initiating treatment with WP1066 may participate. The enzymatic metabolism profile of WP1066 is unknown. Drugs that are minor CYP2D6, 2C9 or 2C19 substrates; minor inhibitors or inducers of CYP2D6, 2C9, or 2C19; or minor substrates of CYP3A4 are allowed. Moderate drugs will be allowed per PI's discretion. Zofran (ondansetron) is allowed
• Patients on corticosteroids who require escalation of the corticosteroid dose Note: Patients receiving a stable or decreasing dose for at least one week may participate. Zofran (ondansetron) is allowed
• History of brain hemorrhage, unless the following exception is met:

Sponsors & Collaborators

• Northwestern University: lead
• Moleculin Biotech, Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Northwestern Medicine: Warrenville

Warrenville, Illinois, 60555, United States

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; Radiotherapy; Radiation; WP1066; Surgical Procedures, Operative

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)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Therapeutics; Physical Phenomena

Study Officials

• Amy Heimberger

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: May 30, 2023
• Study Start: May 22, 2024
• Primary Completion (Estimated): December 27, 2027
• Study Completion (Estimated): December 27, 2028
• Last Updated: December 30, 2025

Record last verified: 2025-12

Locations

US (2)