WP1066 and Radiation Therapy in Newly Diagnosed Glioblastoma Patients

• Status: Not yet recruiting
• Trial end date: 2026-03-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase II, open label, multi-arm trial of radiation therapy in combination with WP1066 in newly diagnosed IDH wild-type, MGMT-unmethylated glioblastoma patients, with multiple cohorts. Patients will be stratified into Cohort 1 versus Cohort 2 based on gross total resection (GTR) status.

Cohort 1: Radiation therapy (RT) + WP1066 in glioblastoma patients with gross total resection Sample size for Cohort 1: Up to 25 patients may be enrolled in order to obtain 21 patients who are evaluable for the primary objective.

Cohort 2: RT + WP1066 ± optional secondary surgical resection post-RT in glioblastoma patients without gross total resection who are candidates for non-emergent palliative surgical resection Sample size for Cohort 2: Up to 14 patients may be enrolled in order to obtain 10 patients who undergo secondary surgical resection.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Moleculin Biotech, Inc.
• Collaborator: Northwestern University

Criteria

Inclusion Criteria:

• Newly diagnosed, histologically confirmed World Health Organization (WHO) glioblastoma multiforme (GBM), IDH wild-type (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.

• 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

• Willing and able to tolerate brain MRI with contrast.

• Karnofsky Performance Scale score ≥ 60%

• Age ≥ 18 years

• Adequate organ and bone marrow function, as defined in Section 3.1, within ≤30 days prior to registration

Exclusion Criteria:

• 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. (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. (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.)

• HIV-positive patients receiving combination antiretroviral therapy (These patients are ineligible because of the potential for pharmacokinetic interactions with WP1066.)

• Patients who have received drugs that significantly interact with CYP450 enzyme(s) within ≤ 2 weeks prior to planned first study treatment day.

• 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.

• Patients on corticosteroids who require escalation of the corticosteroid dose (Patients receiving a stable or decreasing dose for at least one week may participate.)

• Uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs

• Lesion(s) larger than 50 mm in maximal diameter on MRI, or with midline shift exceeding 5 mm, or with hydrocephalus

• Diffuse leptomeningeal disease (Because one of the objectives is PFS based on radiographic volumetric analysis of the tumor, the presence of diffuse leptomeningeal disease is excluded. This is secondary to the inadequacy of measuring the extent of the tumor burden within this setting and the very poor prognosis of these patients.)

• QTc B interval ≥ 450 ms (These patients are excluded because the cardiac toxicities of WP1066 are unknown.)

• Subjects who are at increased risk for radiation therapy (RT)-associated toxicities, such as those with known active collagen vascular disease (e.g., scleroderma, Sjogren's disease, etc.) or other inherited RT-hypersensitivity syndromes (e.g., Gorlin syndrome, Fanconi anemia, ataxia-telangiectasia, etc.)