Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma

NCT06344130 | Recruiting Phase 1

• 2 other identifiers: 10001859001859-C
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Glioblastoma (GBM) is a cancer of the brain. Current survival rates for people with GBM are poor; survival ranges from 5.2 months to 39 months. Most tumors come back within months or years after treatment, and when they do, they are worse: Overall survival drops to less than 10 months. No standard treatment exists for people whose GBM has returned after radiation therapy. Objective: To find a safe schedule for using radiation to treat GBM tumors that returned after initial radiation treatment. Eligibility: People aged 18 years and older with grade 4 GBM that returned after initial radiation treatment. Design: Participants will be screened. They will have a physical exam with blood tests. A sample of tumor tissue may be collected. Participants will undergo re-irradiation planning: They will wear a plastic mask over their head during imaging scans. These scans will pinpoint the exact location of the tumor. This spot will be the target of the radiation treatments. Participants will undergo radiation treatment 4 times per week. Some people will have this treatment for 3 weeks, some for 2 weeks, and some for 1 week. Blood tests and other exams will be repeated at each visit. Participants will complete questionnaires about their physical and mental health. They will answer these questions before starting radiation treatment; once a week during treatment; and at intervals for up to 3 years after treatment ends. Participants will have follow-up visits 1 month after treatment and then every 2 months for 6 months. Follow-up clinic visits will continue up to 3 years. Follow-ups by phone or email will continue an additional 2 years.

Conditions

Astrocytoma; Glioma; Recurrent Glioblastoma

Keywords

Radiotherapy; Hypofractionation; Re-irradiation

Outcome Measures

Primary Outcomes (1)

• MTD of daily re-irradiation in participants with recurrent grade 4 gliomas

  The number of participants experiencing DLTs within the DLT period will be reported for each hypofractionation schema. The MTD will be identified, and the proportion of participants treated with the MTD experiencing DLT will be reported.

  DLT period (28 days)

Secondary Outcomes (6)

• Progression free survival

  Baseline, 30 day safety follow up visit, every 2 months for 2 years, every 3 months for 3rd year, or until progression

• Overall survival

  Treatment and follow up

• Compliance and feasibility of administering PRO in this participant population

  Baseline through 3 years post radiation therapy.

• Tolerability of treatment by assessing adverse events, cognitive function, physical function, and side effect bother

  First radiation treatment administration through 6 months after the last day of radiation. Beyond 6 months after radiation, only adverse events which are serious and related to radiation need to be recorded.

• Longitudinally describe and evaluate disease and treatment-related symptom severity and interference with daily activities

  Baseline through 3 years post radiation therapy.

Study Arms (2)

1/Arm 1

EXPERIMENTAL

Fraction size escalation of 3 planned re-irradiation dose levels.

Radiation: Radiation Therapy

2/Arm 2

EXPERIMENTAL

MTD of re-irradiation dose.

Radiation: Radiation Therapy

Interventions

Radiation Therapy RADIATION

Radiation therapy will be administered via a linear accelerator using 6 megavoltage (MV) photons or greater.

1/Arm 1; 2/Arm 2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of primary glioblastoma or gliosarcoma of the brain, or secondary glioblastoma of the brain due to transformation from a lower grade to a grade 4 tumor.
• Age \>= 18.
• KPS \>= 70%.
• Previous tumor irradiation to curative-intent doses.
• Radiation dose constraints must be achievable based on assessment with MRI and treatment planning CT.
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count (ANC) \>= 1,000/microL
• Platelets \>= 100,000/microL
• Individuals of child-bearing potential (IOCBP) and individuals who can father children must agree to use effective contraception (barrier, hormonal, intrauterine device, surgical sterilization, abstinence) from study entry and through 6 months after the last study treatment (restricted period). Individuals who can father children must not freeze or donate sperm within the same period.
• Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last study treatment.
• The ability of a participant to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Recent systemic therapy prior to the initiation of the study therapy as follows:
• Bevacizumab used for reasons other than tumor progression or symptomatic management within 2 weeks.
• Temozolomide within 2 weeks.
• Cytotoxic chemotherapy within 3 weeks.
• Any investigational agents within 2 weeks.
• Participants who are unable to undergo MRI evaluation or receive gadolinium contrast for any reason.
• Any prior therapy after surgical re-resection or biopsy within 2 weeks prior to the initiation of the study therapy.
• Requiring radiation therapy within 12 months prior to the initiation of study therapy.
• History of prior therapy with Novacure TTF, Gliadel wafers, or GammaTile therapy.
• Positive beta-human chorionic gonadotropin (HCG) pregnancy test performed in individuals of childbearing potential at screening.
• Participants with known or suspected radiation sensitivity syndromes.
• Uncontrolled intercurrent illness evaluated by medical history and physical exam that are not stable and would potentially increase the risk to the participant.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Astrocytoma; Glioma; Glioblastoma

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Peter GK Mathen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Theresa C Cooley Zgela, R.N.

CONTACT

(301) 451-8905; theresa.cooleyzgela@nih.gov

Peter GK Mathen, M.D.

CONTACT

(301) 496-5457; peter.mathen@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2024
• First Posted: April 3, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers after the completion of the primary endpoint.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)