Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma

Trial Title: Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma

NCT ID: NCT06344130

Condition: Astrocytoma
Glioma
Recurrent Glioblastoma

Conditions: Official terms:
Glioblastoma
Astrocytoma
Recurrence

Conditions: Keywords:
Radiotherapy
Hypofractionation
Re-irradiation

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: Radiation Therapy
Description: Radiation therapy will be administered via a linear accelerator using 6 megavoltage (MV) photons or greater.
Arm group label: 1/Arm 1
Arm group label: 2/Arm 2

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.

Detailed description: Background: - Although survival of glioblastoma (GBM) has improved using standard of care chemoradiation, outcomes are still poor. Most patients will recur within months to years, in or adjacent to their previous treatment field. - There is no consensus standard of care for patients with recurrent GBM. Re-resection is recommended, if possible, to improve symptoms and decrease tumor volume. However, this treatment option is possible only in a minority of patients, and for these patients re-irradiation has emerged as a possible treatment. - Modern radiation therapy (RT) techniques allow delivery of re-irradiation while minimizing the dose to previously treated organs at risk (OAR) within the radiation field. - Data from a recently completed clinical trial at our center (16-C-0081, NCT02709226) suggests that the Maximum Tolerated Dose (MTD) of re-irradiation in 350 cGy fractions is 4200 cGy. Objective: -To determine the maximum tolerated dosage of daily re-irradiation in participants with recurrent Grade 4 gliomas Eligibility: - A histologic diagnosis of GBM, gliosarcoma, or transformation, from a lower grade to a grade 4 brain tumor. - Previous glioma irradiation to curative-intent doses. - Age >= 18. - Karnofsky performance scale (KPS) >= 70. Design: - This is a single center phase I trial using a '3 plus 3' design and a three (3) dose level hypofractionation schema to enroll a maximum of 21 evaluable participants. - Prior to radiation therapy, participants will undergo laboratory evaluations, magnetic resonance imaging (MRI), a treatment planning computed tomography (CT), a neurocognitive function assessment, and patient-reported outcome (PRO) questionnaires. - RT will be administered daily 4 days a week for 1, 2, or 3 weeks in the Radiation Oncology Branch, NCI, at NIH. Radiation will be delivered on consecutive days, 4 fractions per week via a linear accelerator using 6 megavoltage (MV) photons or greater. - Follow-up visits following RT are planned at 1 month, every 2 months for years 1-2, and every 3 months for year 3. These visits will be stopped earlier in case of progression. After progression or 3 years of follow-up, participants will be followed remotely for survival until 5 years after treatment completion.

Criteria for eligibility:
Criteria:
- INCLUSION CRITERIA: - 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 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 - Coagulation: Prothrombin time (PT) / Partial thromboplastin time (PTT) within institutional normal range. - Total and direct bilirubin < 2 x institutional upper limit of normal (ULN) - Aspartate aminotransferase (AST) < 2 x institutional ULN - Alanine transaminase (ALT) < 2 x institutional ULN - Serum creatinine < 1.5 mg/dL - Serum albumin >= 0.75 x institutional normal range - Women of child-bearing potential (WOCBP) and men 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). Men must not freeze or donate sperm within the same period. - Breastfeeding participants must be willing to discontinue breastfeeding 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. EXCLUSION CRITERIA: - 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. - History of prior therapy with Novacure TTF, Gliadel wafers, or GammaTile therapy. - Positive beta-human chorionic gonadotropin (HCG) pregnancy test performed in females 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.

Gender: All

Minimum age: 18 Years

Maximum age: 120 Years

Healthy volunteers: No

Locations:

Facility:
Name: National Institutes of Health Clinical Center

Address:
City: Bethesda
Zip: 20892
Country: United States

Status: Recruiting

Contact:
Last name: National Cancer Institute Referral Office

Phone: 888-624-1937

Start date: October 1, 2024

Completion date: December 31, 2027

Lead sponsor:
Agency: National Cancer Institute (NCI)
Agency class: NIH

Source: National Institutes of Health Clinical Center (CC)

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06344130
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_001859-C.html