Dose Escalation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma
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|ClinicalTrials.gov Identifier: NCT02709226|
Recruitment Status : Recruiting
First Posted : March 16, 2016
Last Update Posted : December 21, 2018
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.
To find out the safety and highest tolerated dose of re-irradiation for people who have recurrent glioblastoma.
People ages 18 50 who have glioblastoma that has been treated with radiation but has regrown.
Participants will be screened with:
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:
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:
MRI of the brain.
Quality of life questionnaire
Neuropsychological tests (at some visits)
After 3 years, participants will be contacted by phone each month.
|Condition or disease||Intervention/treatment||Phase|
|Astrocytoma, Grade IV Giant Cell Glioblastoma Glioblastoma Multiforme Gliosarcoma||Radiation: Radiation||Phase 1|
- Although the survival of gliomas has improved, most high grade gliomas will recur in field or adjacent to the treatment field within months to years of the original treatment. In newly diagnosed GBM, the concurrent use of radiation and temozolomide is standard of care.
- Surgical resection upon recurrence is possible in less than 50% of patients. For a significant proportion of recurrent glioma patients in whom reresection is not favourable and for whom systemic options have been exhausted, re-irradiation has emerged as a possible treatment option.
- Using modern precision RT techniques (stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT) or intensity modulated radiation therapy (IMRT), Rapid Arc techniques), re-irradiation has proven a feasible option with possible benefit in outcome as these techniques are often able to minimize dose to previously treated organs at risk in the field (OAR) and treat the recurrence safely.
- Data from multiple retrospective studies has indicated that not only is re-irradiation feasible, but it may actually improve survival in the appropriately selected patient.
The primary objective of this phase I study is to determine maximum tolerated re-irradiation dose (MTD).
- Recurrent glioblastoma or gliosarcoma
- Prior standard radiation therapy to a dose ranging from 50 to 60 Gy at 1.8 to 2 Gy per fraction.
- Prior irradiation > 12 months from enrollment on protocol.
- Age greater than or equal to 18.
- KPS greater than or equal to 70
- Radiation therapy will be administered daily Monday-Friday at Radiation Oncology Branch (ROB), NCI. All the protocol related follow-up appointments will occur at NCI ROB. Radiation therapy dose will be administered on consecutive treatment days, 5 fractions per week via a linear accelerator using 6 MV photons or greater. Using a 3 plus 3 design , and three dose escalation levels, with 6 patients per dose level with 9 total patients at the MTD (provided no DLT), a maximum of 21 evaluable patients will be enrolled.
- Time to progression will be determined by the interval from initiation of treatment on protocol to progression as per RANO criteria.
- Neurologic decline without radiographic evidence of tumor will be designated as treatment related toxicity. Survival duration will be determined by the interval from initiation of treatment on protocol to date of death.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Dose Escalation Trial of Re-Irradiation in Good Prognosis Recurrent Glioblastoma|
|Actual Study Start Date :||June 15, 2016|
|Estimated Primary Completion Date :||October 30, 2020|
|Estimated Study Completion Date :||October 30, 2025|
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 reirradiation 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 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.
- To determine maximum tolerated re-irradiation dose (MTD) [ Time Frame: 1 month after completion of re-irradiation ]The MTD will be based on the assessment of DLT within one month following the re-irradiation, and will be defined as the dose levelat 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 (greater than or equal to 2/3 or greater than or equal to 2/6 patients) having DLT.
- To determine progression free survival and overall survival [ Time Frame: time of progression; time of death ]interval from initiation of treatment on protocol to progression as perRANO criteria Survival duration will be determined by the interval from initiation of treatment on protocol to date of death
- To determine late toxicity secondary to re-irradiation [ Time Frame: Completion of study ]listing of adverse events
- To determine QOL and impact on neurocognition in the settingof re-irradiation of recurrent glioblastoma [ Time Frame: baseline and at each visit ]QOL scores will be summarized at baseline and for each visit. Changesfrom baseline of health-related quality of life questionnaire meanscores will be evaluated
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02709226
|Contact: Theresa Cooley-Zgela, R.N.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Kevin A Camphausen, M.D.||National Cancer Institute (NCI)|