Trial Outcomes & Findings for Low Dose Radiation Therapy for Glioblastoma Multiforme (NCT NCT01466686)
NCT ID: NCT01466686
Last Updated: 2023-07-03
Results Overview
To estimate the response rate to salvage temozolomide plus LDFRT.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
31 participants
Primary outcome timeframe
3, 6 and 12 month follow-up after therapy has been completed
Results posted on
2023-07-03
Participant Flow
1 patient enrolled in the study and then chose to withdraw prior to assignment/treatment. No data was collected for that participant.
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
31
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
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.
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|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Low Dose Radiation Therapy for Glioblastoma Multiforme
Baseline characteristics by cohort
| Measure |
Temozolomide With Low Dose Fractionated Radiation Therapy
n=30 Participants
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.
|
|---|---|
|
Age, Continuous
|
53.74 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
white
|
27 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
black
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
other
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=5 Participants
|
|
met baseline criteria per protocol
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3, 6 and 12 month follow-up after therapy has been completedPopulation: This data was not collected
To estimate the response rate to salvage temozolomide plus LDFRT.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 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
Outcome measures
| Measure |
Temozolomide With Low Dose Fractionated Radiation Therapy
n=30 Participants
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.
|
|---|---|
|
Overall Survival Rate
|
9.6 months
Interval 7.0 to 15.4
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Temozolomide With Low Dose Fractionated Radiation Therapy
n=30 Participants
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.
|
|---|---|
|
Progression Free Survival Rate
|
7.3 months
Interval 5.6 to 11.0
|
SECONDARY outcome
Timeframe: 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 upThe number of patients with grade 3+ hematologic toxicities.
Outcome measures
| Measure |
Temozolomide With Low Dose Fractionated Radiation Therapy
n=30 Participants
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.
|
|---|---|
|
Number of Patients With Hematologic Toxicities
|
8 Participants
|
SECONDARY outcome
Timeframe: 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 upThe number of patients with reported grade 3+ neurologic toxicities
Outcome measures
| Measure |
Temozolomide With Low Dose Fractionated Radiation Therapy
n=30 Participants
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.
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|---|---|
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Number of Patients With Neurologic Toxicity
|
6 Participants
|
Adverse Events
Temozolomide With Low Dose Fractionated Radiation Therapy
Serious events: 30 serious events
Other events: 0 other events
Deaths: 28 deaths
Serious adverse events
| Measure |
Temozolomide With Low Dose Fractionated Radiation Therapy
n=30 participants at risk
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.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
10.0%
3/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
General disorders
Death (Disease Progression)
|
63.3%
19/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
General disorders
Death (NOS)
|
13.3%
4/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Nervous system disorders
Aphasia
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
General disorders
Disease Progression
|
13.3%
4/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
General disorders
Fatigue
|
10.0%
3/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Nervous system disorders
Intraparenchymal Hemorrhage of Brain
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Investigations
Lymphocyte Count Decrease
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Psychiatric disorders
Personality/Behavioral CTC
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Investigations
ALT increased
|
6.7%
2/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Nervous system disorders
Ambulatory Dysfunction / Inability to Walk
|
6.7%
2/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Gastrointestinal disorders
Bowel Incontinence
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Psychiatric disorders
Cognitive Disturbance
|
10.0%
3/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Vascular disorders
DVT (NOS)
|
6.7%
2/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Vascular disorders
DVT (RLE)
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Nervous system disorders
Headache
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Metabolism and nutrition disorders
Hyperglycemia / Elevated Glucose
|
6.7%
2/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Blood and lymphatic system disorders
Leukocytosis
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Investigations
Lymphocyte Count Decreased
|
20.0%
6/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Investigations
Lymphopenia
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Nervous system disorders
Memory Loss
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Nervous system disorders
Motor Neuropathy
|
6.7%
2/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Gastrointestinal disorders
Nausea
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Eye disorders
Ocular-Visual
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Musculoskeletal and connective tissue disorders
Pain (knee)
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Musculoskeletal and connective tissue disorders
Pain (lower back)
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
General disorders
Pain (NOS)
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Investigations
Platelet Count Decreased
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Nervous system disorders
Seizure
|
6.7%
2/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Nervous system disorders
Speech Impairment
|
6.7%
2/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Nervous system disorders
Status Epilepticus
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Ear and labyrinth disorders
Tinnitus
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Renal and urinary disorders
Urinary Incontinence
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Musculoskeletal and connective tissue disorders
Weakness (lower extremity)
|
10.0%
3/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
|
Musculoskeletal and connective tissue disorders
Weakness (NOS)
|
3.3%
1/30 • 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
Other (Not Including Serious) Adverse Events data was not collected.
|
Other adverse events
Adverse event data not reported
Additional Information
Kristin Redmond, MD
Sidney Kimmel Comprehensive Cancer Center @ Johns Hopkins Medicine
Phone: 4109556980
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place