A Study of Bicalutamide With Brain Re-irradiation to Treat Recurrent/Progressive High Grade Glioma

NCT06501911 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 0608-24-FB
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to learn about a type of brain cancer called high-grade glioma. This study is for people who have previously received treatment for brain cancer, but the cancer has come back or gotten worse after treatment. The main question this study aims to answer is: is it safe for participants to take bicalutamide while receiving brain radiation treatment? Participants will:

• Take bicalutamide every day for 6 months
• Receive radiation treatment to the brain
• Keep a diary of the when they take the bicalutamide and any side effects experienced
• Visit the clinic once every 8 weeks for checkups and tests

Conditions

Recurrent Glioblastoma; Recurrent High-grade Glioma

Keywords

Progressive high grade glioma

Outcome Measures

Primary Outcomes (2)

• The incidence of adverse events (AEs) in participants receiving study treatment (combining partial brain re-irradiation with bicalutamide)

  The incidence of adverse events (AEs) will be described for each dose level cohort as well as the two highest dose levels combined. Toxicities will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Toxicities will be graded on a scale ranging from 1 to 5, with higher numbers indicating a higher severity grade.

  Up to 26 months

• The incidence of serious adverse events (SAEs) in participants receiving study treatment (combining partial brain re-irradiation with bicalutamide)

  The incidence of serious adverse events (SAEs) will be described for each dose level cohort as well as the two highest dose levels combined. Toxicities will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Toxicities will be graded on a scale ranging from 1 to 5, with higher numbers indicating a higher severity grade.

  Up to 26 months

Secondary Outcomes (4)

• Rate of objective response (ORR) in participants receiving treatment

  Up to 44 months

• Six-month Progression-free Survival Rate

  Up to 26 months

• The impact of study treatment on quality of survival (Montreal Cognitive Assessment)

  Up to 44 months

• The impact of study treatment on quality of survival (Karnofsky Performance Scale)

  Up to 44 months

Study Arms (1)

Bicalutamide with brain re-irradiation

EXPERIMENTAL

Participants will take oral bicalutamide daily for six (6) months at a starting dose of 150 mg daily. Participants will be enrolled in cohorts of six (6) participants. The dose will be incrementally adjusted based on dose limiting toxicities seen in the previously enrolled cohort until the Maximum Tolerated Dose (MTD) is reached. The MTD is defined as the dose level below the dose at which at least two (2) of six (6) participants experienced a dose limiting toxicity. Participants will also receive 10 fractions of brain re-irradiation beginning one week after the start of bicalutamide treatment.

Drug: Bicalutamide; Radiation: Intensity-modulated radiation therapy (IMRT)

Interventions

Bicalutamide DRUG

Participants will receive daily oral bicalutamide for six (6) months. The dose will be determined by the cohort to which the participant is enrolled as well as the toxicities experienced by previously enrolled cohorts.

Also known as: Casodex

Bicalutamide with brain re-irradiation

Intensity-modulated radiation therapy (IMRT) RADIATION

Participants will receive 35 Gy delivered in 10 fractions, administered once daily on weekdays.

Also known as: Three-Dimensional Conformal Radiation Therapy (3D-CRT)

Bicalutamide with brain re-irradiation

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically proven diagnosis of relapsed/refractory high-grade glioma (HGG) including glioblastoma or variants (gliosarcoma, giant cell glioblastoma etc), World Health Organization (WHO) grade IV, or anaplastic astrocytoma, or anaplastic oligodendroglioma, WHO grade III. Participants will be eligible if the original histology was lower-grade glioma and a subsequent diagnosis of HGG (secondary HGG) is made.
• Participants who did not have surgery for their HGG within 5 weeks prior to enrollment must have shown unequivocal radiographic evidence for tumor progression by contrast-enhanced magnetic resonance imaging (MRI) scan (or CT scan for participants with non-compatible devices). Imaging completed prior to enrollment will be acceptable for eligibility purposes if completed within 4 weeks prior to enrollment. If imaging was not completed within 4 weeks prior to enrollment then imaging must be completed within 14 days after enrollment and prior to the start of RT.
• Participants unable to undergo magnetic resonance (MR) imaging because of non-compatible devices can be enrolled provided CT scans are obtained and are of sufficient quality. Participants without non-compatible devices may not use CT scans performed to meet this requirement.
• Participants must have passed an interval of 6 months or greater between completion of prior radiotherapy and enrollment. If participants have not passed an interval of at least 6 months, they may still be eligible if they meet one or more of the following criteria:
• New areas of tumor outside the original radiotherapy fields as determined by the investigator
• Histologic confirmation of tumor through biopsy or resection
• Nuclear medicine imaging, MR spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than radiation necrosis obtained within 28 days of registration AND an interval of at least 90 days between completion of previous radiotherapy and registration
• Prior history of standard dose central nervous system (CNS) radiation of 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent or lower doses.
• Participants must have recovered from the toxic effects of prior chemotherapy, and there must be a minimum time of 14 days prior to enrollment from the administration of any investigational agent or prior cytotoxic therapy with the following exceptions:
• days from administration of vincristine
• days from administration of nitrosoureas
• days from administration of procarbazine
• Participants having undergone recent resection of their glioblastoma (within 5 weeks prior to enrollment) must have recovered from the effects of surgery. For CNS related core or needle biopsies, a minimum of 7 days must have elapsed prior to enrollment.
• Residual disease following resection of recurrent glioblastoma is not mandated for eligibility into the study.
• History/physical examination, including neurologic examination, within 14 days prior to enrollment

You may not qualify if:

• Infratentorial, or diffuse leptomeningeal evidence of recurrent disease. If focal leptomeningeal disease (per treating physician's determination of being "focal"), participants can be considered eligible.
• Ongoing therapy with any androgen deprivation therapy (ADT) such as leuprolide acetate, degarelix, bicalutamide, flutamide, enzalutamide, apalutamide, abiraterone acetate, darolutamide or others per principal investigator's determination. If ADT has been stopped prior to the enrollment, at least 6 months of ADT-free time is required for eligibility.
• Prior allergic reaction to the drug bicalutamide 3.2.4 Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year (for example, carcinoma in situ of the breast, oral cavity, prostate, or cervix are all permissible).
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration.
• Congestive heart failure (NYHA functional capacity class II or greater).
• Transmural myocardial infarction within the last 6 months prior to registration.
• History of stroke or transient ischemic attack within 6 months prior to registration.
• Ongoing arrhythmias of Grade \>2 \[CTCAE, version 5.0\]; Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
• Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism) in the past 6 months.
• Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
• Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. 3.2.6 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
• Known Acquired Immune Deficiency Syndrome (AIDS) diagnosis based upon current Centers for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude participants with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
• Immuno-compromised participants with transplant in history are excluded.

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

bicalutamide; Radiotherapy, Intensity-Modulated; Radiotherapy, Conformal

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Chi Zhang, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2024
• First Posted: July 15, 2024
• Study Start: April 8, 2025
• Primary Completion: July 17, 2025
• Study Completion: July 17, 2025
• Last Updated: July 22, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)