High Grade Glioma
Conditions
Keywords
Recurrent Glioblastoma Multiforme, Recurrent Anaplastic Astrocytoma, Surgery, Adjuvant Radiation, Adjuvant Temozolomide
Brief summary
To evaluate the safety and effectiveness of low dose rate radiation therapy plus temozolomide. This will be in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) who have previously been treated with surgery followed by radiation surgical resection followed by adjuvant radiation therapy plus temozolomide.
Detailed description
In vitro and in vivo studies have suggested that low dose fractionated radiation therapy (LDFRT) may be used to potentiate full dose chemotherapy, decreasing the development of resistance found with standard doses of radiation and chemotherapy. This is a nonrandomized, open label, single institution phase II trial with a safety run-in to evaluate the safety and efficacy of LDFRT plus temozolomide in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) previously treated with surgical resection followed by adjuvant radiation therapy plus temozolomide. The primary objective of the phase II study is to estimate response rate in patients treated with twice daily fractions of low dose radiation plus temozolomide chemotherapy.
Interventions
All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below.
DRUGTemozolomide
All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have recurrent GBM (Glioblastoma Multiforme)or Anaplastic Astrocytoma. * The diagnosis of GBM or Anaplastic Astrocytoma. * Patients must have been previously treated with surgical resection (any extent okay) and adjuvant radiation therapy plus temozolomide. * Patients must be at least 12 months from completion of radiation therapy * At least 2 months from completion of temozolomide (to be consistent with the the rechallenge group from Perry et al. JCO 2010). * Age \>18 years * ECOG performance status \<2 (Karnofsky \>60%, see appendix A). * There must be measurable disease on MRI. * Patients must have normal organ and marrow function as defined below: * Women must not be pregnant * Ability to understand and the willingness to sign a written informed consent document * Temozolomide re-treatment is planned by the treating neuro-oncologist. * The most recent brain tumor pathology obtained for the patient must be glioblastoma.
Exclusion criteria
* Must be able to receive an MRI * Patients may not be receiving any other investigational cancer treatment agents at the time of enrollment. * Patients may not have previously failed treatment with salvage temozolomide. * Patients may not have previously failed treatment with a VEGF inhibitor. * Patients may not have previously been treated with \>1 course of radiotherapy. * Patients may not have previously been treated with radiosurgery to the brain. * Uncontrolled intercurrent illness * Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use and acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. Male subjects must also agree to use effective contraception for the same period as above.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate | up to 12 months after completion of temozolomide (48 weeks of treatment) | Overall survival rate is calculated as the median number of months that patients were alive for the cohort |
| Response Rate | 3, 6 and 12 month follow-up after therapy has been completed | To estimate the response rate to salvage temozolomide plus LDFRT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Rate | up to 12 months after completion of temozolomide (48 weeks of treatment) | Progression free survival rate is calculated as the median number of months for the cohort until patient's disease worsened/progressed |
| Number of Patients With Hematologic Toxicities | Approximately every month from study start until 48 weeks, and then up to 12 months after completion of temozolomide at 3, 6, and 12 months follow up | The number of patients with grade 3+ hematologic toxicities. |
| Number of Patients With Neurologic Toxicity | Approximately every month from study start until 48 weeks, and then up to 12 months after completion of temozolomide at 3, 6, and 12 months follow up | The number of patients with reported grade 3+ neurologic toxicities |
Countries
United States
Participant flow
Pre-assignment details
1 patient enrolled in the study and then chose to withdraw prior to assignment/treatment. No data was collected for that participant.
Participants by arm
| Arm | Count |
|---|---|
| Temozolomide With Low Dose Fractionated Radiation Therapy All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.
All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below. Otherwise, following a 1 month waiting period after the first cycle of adjuvant LDFRT plus temozolomide for the first cohort of patients, the phase 2 study will open for full accrual. Patients will receive radiation with the first six 28-day cycles of temozolomide.
Low Dose Fractionated Radiation Therapy (LDFRT): All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If \> 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below.
Temozolomide: All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Temozolomide With Low Dose Fractionated Radiation Therapy |
|---|---|
| Age, Continuous | 53.74 years |
| met baseline criteria per protocol | 30 Participants |
| Race/Ethnicity, Customized black | 2 Participants |
| Race/Ethnicity, Customized other | 1 Participants |
| Race/Ethnicity, Customized white | 27 Participants |
| Region of Enrollment United States | 30 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 28 / 30 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 30 / 30 |
Outcome results
Primary
Overall Survival Rate
Overall survival rate is calculated as the median number of months that patients were alive for the cohort
Time frame: up to 12 months after completion of temozolomide (48 weeks of treatment)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Temozolomide With Low Dose Fractionated Radiation Therapy | Overall Survival Rate | 9.6 months |
Primary
Response Rate
To estimate the response rate to salvage temozolomide plus LDFRT.
Time frame: 3, 6 and 12 month follow-up after therapy has been completed
Population: This data was not collected
Secondary
Number of Patients With Hematologic Toxicities
The number of patients with grade 3+ hematologic toxicities.
Time frame: Approximately every month from study start until 48 weeks, and then up to 12 months after completion of temozolomide at 3, 6, and 12 months follow up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Temozolomide With Low Dose Fractionated Radiation Therapy | Number of Patients With Hematologic Toxicities | 8 Participants |
Secondary
Number of Patients With Neurologic Toxicity
The number of patients with reported grade 3+ neurologic toxicities
Time frame: Approximately every month from study start until 48 weeks, and then up to 12 months after completion of temozolomide at 3, 6, and 12 months follow up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Temozolomide With Low Dose Fractionated Radiation Therapy | Number of Patients With Neurologic Toxicity | 6 Participants |
Secondary
Progression Free Survival Rate
Progression free survival rate is calculated as the median number of months for the cohort until patient's disease worsened/progressed
Time frame: up to 12 months after completion of temozolomide (48 weeks of treatment)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Temozolomide With Low Dose Fractionated Radiation Therapy | Progression Free Survival Rate | 7.3 months |