Trial Outcomes & Findings for Gliadel, XRT, Temodar, Avastin Followed by Avastin, Temodar for Newly Diagnosed Glioblastoma Multiforme (GBM) (NCT NCT01186406)
NCT ID: NCT01186406
Last Updated: 2019-02-15
Results Overview
The percentage of participants alive at 21 months after the start of study treatment. Overall survival was calculated from the date study treatment started until the date of death or the date of last follow-up if alive. Kaplan-Meier methods were used to estimate overall survival.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
41 participants
Primary outcome timeframe
21 months
Results posted on
2019-02-15
Participant Flow
Study recruitment was stopped early due to unacceptable toxicity after 41 participants were enrolled.
Forty-seven subjects were consented to the study. Six subjects were screen failures and were not enrolled.
Participant milestones
| Measure |
Gliadel, Radiation Therapy, Avastin, Temodar
Single arm study where patients with newly diagnosed Grade IV malignant glioma will receive Gliadel at the time of resection, followed by radiation therapy (XRT), Avastin, and Temodar for approximately 6 1/2 weeks, followed by Avastin and Temodar post-radiation
Gliadel, Radiation Therapy, Avastin, Temodar: Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, they will be treated with standard radiation therapy, and daily Temodar (75mg/m2) for 6.5 weeks of radiation. In addition, Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively.
Beginning 2-3 weeks after the last radiation therapy, but not greater than 8 weeks, patients will be treated with Avastin (10 mg/kg) every 14 days along with 5 day Temodar (200 mg/ m2).
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|---|---|
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Overall Study
STARTED
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41
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Overall Study
COMPLETED
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41
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Gliadel, XRT, Temodar, Avastin Followed by Avastin, Temodar for Newly Diagnosed Glioblastoma Multiforme (GBM)
Baseline characteristics by cohort
| Measure |
Gliadel, Radiation Therapy, Avastin, Temodar
n=41 Participants
Single arm study where patients with newly diagnosed Grade IV malignant glioma will receive Gliadel at the time of resection, followed by radiation therapy (XRT), Avastin, and Temodar for approximately 6 1/2 weeks, followed by Avastin and Temodar post-radiation Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy. Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively. Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation.
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|---|---|
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Age, Continuous
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57.2 years
STANDARD_DEVIATION 10.7 • n=99 Participants
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Sex: Female, Male
Female
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13 Participants
n=99 Participants
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Sex: Female, Male
Male
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28 Participants
n=99 Participants
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PRIMARY outcome
Timeframe: 21 monthsPopulation: Intent-to-treat
The percentage of participants alive at 21 months after the start of study treatment. Overall survival was calculated from the date study treatment started until the date of death or the date of last follow-up if alive. Kaplan-Meier methods were used to estimate overall survival.
Outcome measures
| Measure |
Gliadel, Radiation Therapy, Avastin, Temodar
n=41 Participants
Single arm study where patients with newly diagnosed Grade IV malignant glioma will receive Gliadel at the time of resection, followed by radiation therapy (XRT), Avastin, and Temodar for approximately 6 1/2 weeks, followed by Avastin and Temodar post-radiation. Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy. Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively. Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation.
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21-month Overall Survival
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40.9 percentage of participants
Interval 25.8 to 55.5
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SECONDARY outcome
Timeframe: 21 monthsPopulation: Intent-to-treat
Overall survival was defined as the time in months from the start of SRS to the date of death or last contact if alive. Kaplan-Meier methods were used to estimate overall survival.
Outcome measures
| Measure |
Gliadel, Radiation Therapy, Avastin, Temodar
n=41 Participants
Single arm study where patients with newly diagnosed Grade IV malignant glioma will receive Gliadel at the time of resection, followed by radiation therapy (XRT), Avastin, and Temodar for approximately 6 1/2 weeks, followed by Avastin and Temodar post-radiation. Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy. Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively. Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation.
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Median Overall Survival
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19.4 months
Interval 16.1 to 21.9
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SECONDARY outcome
Timeframe: 21 monthsPopulation: Intent-to-treat
Progression-free survival was defined as the time in months from the date study treatment started until the date of progression or the date of death if death occurred before progression, or until the date of last follow-up if alive without progression. Kaplan-Meier methods were used to estimate progression-free survival.
Outcome measures
| Measure |
Gliadel, Radiation Therapy, Avastin, Temodar
n=41 Participants
Single arm study where patients with newly diagnosed Grade IV malignant glioma will receive Gliadel at the time of resection, followed by radiation therapy (XRT), Avastin, and Temodar for approximately 6 1/2 weeks, followed by Avastin and Temodar post-radiation. Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy. Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively. Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation.
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|---|---|
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Median Progression-free Survival
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11.3 months
Interval 9.2 to 14.2
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SECONDARY outcome
Timeframe: 27 monthsThe number of patients experiencing unacceptable toxicity defined as the occurrence of ≥ grade 2 CNS hemorrhage or treatment-related grade 4 or 5 non-hematologic toxicity.
Outcome measures
| Measure |
Gliadel, Radiation Therapy, Avastin, Temodar
n=41 Participants
Single arm study where patients with newly diagnosed Grade IV malignant glioma will receive Gliadel at the time of resection, followed by radiation therapy (XRT), Avastin, and Temodar for approximately 6 1/2 weeks, followed by Avastin and Temodar post-radiation. Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy. Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively. Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation.
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Unacceptable Toxicity Related to the Treatment Regimen
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6.0 Participants
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Adverse Events
Gliadel, Radiation Therapy, Avastin, Temodar
Serious events: 18 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Gliadel, Radiation Therapy, Avastin, Temodar
n=41 participants at risk
Single arm study where patients with newly diagnosed Grade IV malignant glioma will receive Gliadel at the time of resection, followed by radiation therapy (XRT), Avastin, and Temodar for approximately 6 1/2 weeks, followed by Avastin and Temodar post-radiation. Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy. Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively. Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation.
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|---|---|
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Gastrointestinal disorders
Dysphagia
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Gastrointestinal disorders
Enterocolitis
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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General disorders
Death NOS
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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General disorders
Fatigue
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4.9%
2/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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General disorders
Fever
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Infections and infestations
Infections and infestations - Other, specify
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Infections and infestations
Meningitis
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Infections and infestations
Wound infection
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Metabolism and nutrition disorders
Dehydration
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Musculoskeletal and connective tissue disorders
Generalized muscle weakness
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9.8%
4/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Musculoskeletal and connective tissue disorders
Muscle weakness right-sided
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Nervous system disorders
Cognitive disturbance
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4.9%
2/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Nervous system disorders
Depressed level of consciousness
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7.3%
3/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Nervous system disorders
Edema cerebral
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7.3%
3/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Nervous system disorders
Headache
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4.9%
2/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Nervous system disorders
Seizure
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14.6%
6/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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|
Nervous system disorders
Stroke
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4.9%
2/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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|
Psychiatric disorders
Confusion
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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|
Vascular disorders
Thromboembolic event
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9.8%
4/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
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Other adverse events
| Measure |
Gliadel, Radiation Therapy, Avastin, Temodar
n=41 participants at risk
Single arm study where patients with newly diagnosed Grade IV malignant glioma will receive Gliadel at the time of resection, followed by radiation therapy (XRT), Avastin, and Temodar for approximately 6 1/2 weeks, followed by Avastin and Temodar post-radiation. Patients will have 1-8 wafers of Gliadel inserted at the time of surgical resection. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy. Avastin (10 mg/kg) will be given every 14 days, and will begin a minimum of 42 days post-operatively. Beginning two to three weeks after the last radiation therapy, but not greater than eight weeks, subjects will be treated with Avastin (10mg/m2) every 14 days. At a minimum of four weeks, but not greater than eight weeks post-craniotomy, subjects will be treated with standard radiation therapy and daily Temodar (75mg/m2) for 6.5 weeks of the radiation.
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|---|---|
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General disorders
Fatigue
|
4.9%
2/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Infections and infestations
Meningitis
|
2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Infections and infestations
Tooth Infection
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2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Infections and infestations
Wound infection
|
4.9%
2/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Investigations
Neutrophil count decreased
|
4.9%
2/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Investigations
Platelet count decreased
|
12.2%
5/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Investigations
White blood cell decreased
|
2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
14.6%
6/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
4.9%
2/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Psychiatric disorders
Psychosis
|
2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Renal and urinary disorders
Proteinuria
|
2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Vascular disorders
Hypertension
|
2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
|
Vascular disorders
Thromboembolic event
|
2.4%
1/41 • From the start of study treatment for a patient until 30 days after treatment is discontinued.
Patients will be evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation. After evaluation, all adverse events graded 3 and above, and all serious adverse events will be captured in the study database.
|
Additional Information
Annick Desjardins, MD, FRCPC
Duke University Medical Center
Phone: 9196846173
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place