Dose Escalation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma

NCT02709226 | Completed Phase 1

• 2 other identifiers: 16008116-C-0081
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Background: A glioblastoma is a tumor in the brain. It is treated with surgery, chemotherapy and radiation therapy. However, most people s tumors come back after therapy. When the tumor grows back, surgery or chemotherapy may not be possible or may no longer work. Repeat radiation therapy or re-irradiation, is an option for treating these tumors when they regrow. Objective: To find out the safety and highest tolerated dose of re-irradiation for people who have recurrent glioblastoma. Eligibility: People ages 18 50 who have glioblastoma that has been treated with radiation but has regrown. Design: Participants will be screened with: Medical history Physical exam MRI of the brain: They will lie in a machine that takes pictures of the brain. Participants will have baseline tests before they start therapy. These will include: Blood tests Neuropsychological tests: These test things like memory, attention, and thinking. Quality of life questionnaire Eye and hearing tests Participants will get a CT of the brain prior to radiation start in order to plan the radiation treatment. Once the plan is completed, they will receive radiation once a day Monday Friday for a total of 10 17 treatments. They will lie on their back for about 10 minutes while they get the treatment. Participants will be monitored for side effects. After they finish treatment, participants will have visits 1, 2, and 3 months later. Then they will have them every 2 months for 3 years. These will include: Medical history Physical exam Blood tests MRI of the brain. Quality of life questionnaire Neuropsychological tests (at some visits) After 3 years, participants will be contacted by phone each month.

Conditions

Astrocytoma, Grade IV; Giant Cell Glioblastoma; Glioblastoma Multiforme; Gliosarcoma

Keywords

Brain Tumor; Astrocytoma; GBM; Radiation Therapy

Outcome Measures

Primary Outcomes (1)

• To determine maximum tolerated re-irradiation dose (MTD).

  The MTD will be based on the assessment of DLT within one month following the re-irradiation, and will be defined as the dose level at which less than one-third of patients (0/3 or 0-1/6 patients) treated at that dose experience a DLT, with the next higher dose level demonstrating a one-third or greater number of patients (\>= 2/3 or \>= 2/6 patients) having DLT.

  1 month after completion of re-irradiation

Secondary Outcomes (3)

• To determine QOL and impact on neurocognition in the setting of re-irradiation of recurrent glioblastoma

  baseline and at each visit

• To determine progression free survival and overall survival.

  time of progression; time of death

• To determine late toxicity secondary to re-irradiation

  completion of study

Study Arms (1)

1/Radiation

EXPERIMENTAL

Dose escalation is as follows: dose level 1 (DL1) 3.5 Gy x 10; dose level 2 (DL2) 3.5 Gy x 12; dose level 3 (DL3) 3.5 Gy x 14. If 2 DLTs are observed in the second dose level a step down dose of 3.0 Gy x 14 fractions will be tested. If 2 DLTs are observed in the third dose level a step down dose of 3.0 Gy x 17 fractions will be tested. The study will have 3 planned re-irradiation dose levels, with 1 to 6 patients per dose level using the 3+3 design to define the MTD. The number of patients may be increased to 9 total patients at the MTD ( provided no DLT) with a maximum of 21 evaluable patients enrolled.

Radiation: Radiation

Interventions

Radiation RADIATION

Radiation therapy will be administered daily Monday-Friday at NCI, ROB unless the treatment schedule requires amendment in the event of inclement weather or federal holidays. Radiation therapy dose will be administered as per on consecutive treatment days, 5 fractions per week via a linear accelerator using 6 MV photons or greater. Dose escalation is as follows: dose level 1 (DL1) 3.5 Gy x 10; dose level 2 (DL2) 3.5 Gy x 12; dose level 3 (DL3) 3.5 Gy x 14. If 2 DLTs are observed in the second dose level a step down dose of 3.0 Gy x 14 fractions will be tested. If 2 DLTs are observed in the third dose level a step down dose of 3.0 Gy x 17 fractions will be tested. The study will have 3 planned re-irradiation dose levels, with 1 to 6 patients per dose level using the 3+3 design to define the MTD. The number of patients may be increased to 9 total patients at the MTD ( provided no DLT) with a maximum of 21 evaluable patients enrolled.

1/Radiation

Eligibility Criteria

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

You may qualify if:

• Histological diagnosis
• Previous histologic diagnosis of glioblastoma, transformation to glioblastoma or gliosarcoma established by biopsy or resection prior to enrollment as evident on NIH or outside pathology.
• Patients must be age greater than or equal to 18.
• Patients should have a KPS greater than or equal to 70%
• Prior standard radiation therapy to a dose ranging from 50 to 60 Gy at 1.8 to 2 Gy per fraction.
• Patients must be more than or equal to 14 days from previous cytotoxic treatment.
• Concurrent therapy
• The concurrent use of bevacizumab is allowed if previously initiated for tumor progression or symptomatic management. Prior temozolomide or other cytotoxic chemotherapy is allowed.
• Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

You may not qualify if:

• Prior therapy \< than 2 weeks since surgical re-resection or biopsy
• Pregnant or breast feeding females are excluded due to potential mutagenic effects on the developing fetus or newborn
• Preexisting grade 3 or 4 nervous system disorder as per CTCAE Version 4.0
• Clinically significant unrelated systemic illness (including but not limited to active life threatening infection, cardiac or neurologic events, current hospital admission for a coexisting comorbid illness), which would make it impossible for the patient to tolerate re-irradiation or systemic chemotherapy or likely to interfere with the results.
• Patients exhibiting baseline grade 3 or 4 by CTCAE criteria are excluded due to difficulty in assigning these to the study intervention as treatment related DLT.
• Patients with preexisting known or suspected radiation sensitivity syndromes will be excluded due to potential confounding effect on outcome.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms; Astrocytoma

Interventions

Radiation

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

• Kevin A Camphausen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 15, 2016
• First Posted: March 16, 2016
• Study Start: June 15, 2016
• Primary Completion: December 16, 2022
• Study Completion: July 19, 2023
• Last Updated: December 31, 2025

Record last verified: 2025-12-16

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)