Trial Outcomes & Findings for Vorinostat, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (NCT NCT00731731)
NCT ID: NCT00731731
Last Updated: 2022-08-04
Results Overview
The Maximum Tolerated Dose (MTD) will be based on the assessment of Dose Limiting Toxicity (DLT) during the first 10 weeks of treatment only, and will be defined as the dose at which fewer than one-third of patients experience a DLT to vorinostat. The MTD is the dose level at which 0/3 or 1/6 patients experience DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT. \> \> DLT will be defined as any of the following events occurring during treatment with vorinostat and temozolomide and attributable to one or both study drugs: * Grade 3 or 4 thrombocytopenia, grade 4 anemia or grade 4 neutropenia lasting \> 7 days * Any non-hematologic grade 3 or greater adverse event, excluding alopecia and venous thromboembolism * Grade 4 radiation-induced skin changes * Failure to recover from toxicities to be eligible for re-treatment with vorinostat and temozolomide ≤ 14 days of the last dose of the two drugs
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
125 participants
Primary outcome timeframe
10 weeks
Results posted on
2022-08-04
Participant Flow
Participant milestones
| Measure |
Phase I, Dose Level 0
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD (every day) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase I, Dose Level 1
Patients undergo 60 Gy radiotherapy and receive 400 mg vorinostat PO QD (every day) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase II
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD (every day) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 400 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5 for cycle 2 and 200 mg/m2 temozolomide PO QD on days 1-5 for all subsequent cycles. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
|---|---|---|---|
|
Overall Study
STARTED
|
12
|
3
|
110
|
|
Overall Study
COMPLETED
|
12
|
3
|
107
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
3
|
Reasons for withdrawal
| Measure |
Phase I, Dose Level 0
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD (every day) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase I, Dose Level 1
Patients undergo 60 Gy radiotherapy and receive 400 mg vorinostat PO QD (every day) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase II
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD (every day) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 400 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5 for cycle 2 and 200 mg/m2 temozolomide PO QD on days 1-5 for all subsequent cycles. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
|---|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
|
Overall Study
Cancel prior to treatment
|
0
|
0
|
2
|
Baseline Characteristics
Vorinostat, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Baseline characteristics by cohort
| Measure |
Phase I, Dose Level 0
n=12 Participants
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.\>
* dimensional conformal radiation therapy: Undergo radiotherapy\> \> temozolomide: Given PO\> \> vorinostat: Given PO\> \> cognitive assessment: Ancillary studies\> \> laboratory biomarker analysis: Correlative studies
|
Phase I, Dose Level 1
n=3 Participants
Patients undergo 60 Gy radiotherapy and receive 400 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.\>
* dimensional conformal radiation therapy: Undergo radiotherapy\> \> temozolomide: Given PO\> \> vorinostat: Given PO\> \> cognitive assessment: Ancillary studies\> \> laboratory biomarker analysis: Correlative studies
|
Phase II
n=107 Participants
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 400 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5 for cycle 2 and 200 mg/m2 temozolomide PO QD on days 1-5 for all subsequent cycles. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.\>
* dimensional conformal radiation therapy: Undergo radiotherapy\> \> temozolomide: Given PO\> \> vorinostat: Given PO\> \> cognitive assessment: Ancillary studies\> \> laboratory biomarker analysis: Correlative studies
|
Total
n=122 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57 years
n=5 Participants
|
59 years
n=7 Participants
|
59 years
n=5 Participants
|
59 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
51 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
71 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
114 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 10 weeksThe Maximum Tolerated Dose (MTD) will be based on the assessment of Dose Limiting Toxicity (DLT) during the first 10 weeks of treatment only, and will be defined as the dose at which fewer than one-third of patients experience a DLT to vorinostat. The MTD is the dose level at which 0/3 or 1/6 patients experience DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT. \> \> DLT will be defined as any of the following events occurring during treatment with vorinostat and temozolomide and attributable to one or both study drugs: * Grade 3 or 4 thrombocytopenia, grade 4 anemia or grade 4 neutropenia lasting \> 7 days * Any non-hematologic grade 3 or greater adverse event, excluding alopecia and venous thromboembolism * Grade 4 radiation-induced skin changes * Failure to recover from toxicities to be eligible for re-treatment with vorinostat and temozolomide ≤ 14 days of the last dose of the two drugs
Outcome measures
| Measure |
Phase I, Dose Level 0
n=12 Participants
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase I, Dose Level 1
n=3 Participants
Patients undergo 60 Gy radiotherapy and receive 400 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase II
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 400 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5 for cycle 2 and 200 mg/m2 temozolomide PO QD on days 1-5 for all subsequent cycles. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
|---|---|---|---|
|
Maximum Tolerated Dose of Vorinostat, Defined as the Dose at Which Fewer Than One-third of Patients Experience DLTs, Graded According to NCI CTCAE (Common Toxicity Criteria for Adverse Effects) Version 3.0 (Phase I)
|
3 number of patients with DLT
|
3 number of patients with DLT
|
—
|
PRIMARY outcome
Timeframe: Time from study registration to the date of death from any cause, assessed up to 5 yearsThe primary endpoint will be survival status at 15 months (OS15). In addition, survival will be estimated using a Kaplan-Meier curve. For this analysis, patients who are still alive at the time of analysis have survival time censored at the last contact date.
Outcome measures
| Measure |
Phase I, Dose Level 0
n=107 Participants
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase I, Dose Level 1
Patients undergo 60 Gy radiotherapy and receive 400 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase II
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 400 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5 for cycle 2 and 200 mg/m2 temozolomide PO QD on days 1-5 for all subsequent cycles. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
|---|---|---|---|
|
Overall Survival at 15 Months (Phase II)
|
54.6 percentage of phase II patients
Interval 45.9 to 65.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsSafety variables will be summarized by descriptive statistics. Adverse Events (AEs) that occur will be reported for each phase and dose level and described in terms of incidence and severity. Parameters will be described based on the CTC severity grading. Distribution by CTC severity grade and clinical relevance will be given.
Outcome measures
| Measure |
Phase I, Dose Level 0
n=12 Participants
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase I, Dose Level 1
n=3 Participants
Patients undergo 60 Gy radiotherapy and receive 400 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase II
n=107 Participants
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 400 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5 for cycle 2 and 200 mg/m2 temozolomide PO QD on days 1-5 for all subsequent cycles. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
|---|---|---|---|
|
Incidence of Adverse Events, Based on CTC (Common Toxicity Criteria) Severity Grade
|
12 participants evaluable for toxicity
|
3 participants evaluable for toxicity
|
107 participants evaluable for toxicity
|
SECONDARY outcome
Timeframe: Up to 5 yearsProgression free survival time will be defined from date of registration to date of progression or death.
Outcome measures
| Measure |
Phase I, Dose Level 0
n=107 Participants
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase I, Dose Level 1
Patients undergo 60 Gy radiotherapy and receive 400 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase II
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 400 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5 for cycle 2 and 200 mg/m2 temozolomide PO QD on days 1-5 for all subsequent cycles. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
|---|---|---|---|
|
Time to Tumor Progression (Phase II)
|
8.05 months
Interval 6.21 to 9.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsThe maximum grade for each type of treatment-related adverse event will be recorded for each patient, and frequency tables for each arm will be reviewed to determine patterns. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.
Outcome measures
| Measure |
Phase I, Dose Level 0
n=12 Participants
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase I, Dose Level 1
n=3 Participants
Patients undergo 60 Gy radiotherapy and receive 400 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 500 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
Phase II
n=107 Participants
Patients undergo 60 Gy radiotherapy and receive 300 mg vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive 75 mg/m2 temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive 400 mg vorinostat PO QD on days 1-7 and 15-21 and 150 mg/m2 temozolomide PO QD on days 1-5 for cycle 2 and 200 mg/m2 temozolomide PO QD on days 1-5 for all subsequent cycles. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* dimensional conformal radiation therapy: Undergo radiotherapy \> \> temozolomide: Given PO \> \> vorinostat: Given PO \> \> cognitive assessment: Ancillary studies \> \> laboratory biomarker analysis: Correlative studies
|
|---|---|---|---|
|
Incidence of Adverse Events, as Per NCI CTCAE Version 3.0 (Phase II)
|
12 participants evaluable for toxicity
|
3 participants evaluable for toxicity
|
107 participants evaluable for toxicity
|
Adverse Events
Phase I, Dose Level 0
Serious events: 11 serious events
Other events: 12 other events
Deaths: 0 deaths
Phase I, Dose Level 1
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase II
Serious events: 63 serious events
Other events: 106 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I, Dose Level 0
n=12 participants at risk
laboratory biomarker analysis: Correlative studies
|
Phase I, Dose Level 1
n=3 participants at risk
laboratory biomarker analysis: Correlative studies
|
Phase II
n=107 participants at risk
laboratory biomarker analysis: Correlative studies
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Blood disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 4
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
8.3%
1/12 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
10.3%
11/107 • Number of events 26
|
|
Cardiac disorders
Atrial tachycardia
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Gastrointestinal disorders
Colonic perforation
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 6
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
0.93%
1/107 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
General disorders
Edema limbs
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 3
|
|
General disorders
Fatigue
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
9.3%
10/107 • Number of events 17
|
|
General disorders
Flu-like symptoms
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
General disorders
General symptom
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
General disorders
Localized edema
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Infections and infestations
Infection
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Infections and infestations
Opportunistic infection
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Infections and infestations
Sepsis
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Infections and infestations
Skin infection
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Injury, poisoning and procedural complications
Aortic injury
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Injury, poisoning and procedural complications
Intraoperative neurological injury
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Injury, poisoning and procedural complications
Vascular access complication
|
0.00%
0/12
|
0.00%
0/3
|
3.7%
4/107 • Number of events 7
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/12
|
0.00%
0/3
|
7.5%
8/107 • Number of events 13
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/12
|
0.00%
0/3
|
4.7%
5/107 • Number of events 6
|
|
Investigations
Bilirubin increased
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 4
|
|
Investigations
Creatinine increased
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 3
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Investigations
Laboratory test abnormal
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
8.3%
1/12 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
17.8%
19/107 • Number of events 54
|
|
Investigations
Lipase increased
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Investigations
Lymphocyte count decreased
|
33.3%
4/12 • Number of events 4
|
0.00%
0/3
|
16.8%
18/107 • Number of events 61
|
|
Investigations
Neutrophil count decreased
|
8.3%
1/12 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
15.9%
17/107 • Number of events 47
|
|
Investigations
Platelet count decreased
|
33.3%
4/12 • Number of events 4
|
33.3%
1/3 • Number of events 1
|
23.4%
25/107 • Number of events 81
|
|
Investigations
Weight loss
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 11
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
4.7%
5/107 • Number of events 14
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
4.7%
5/107 • Number of events 11
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 3
|
|
Metabolism and nutrition disorders
Serum phosphate decreased
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
0.93%
1/107 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness left-sided
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness right-sided
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Nervous system disorders
Cognitive disturbance
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Nervous system disorders
Neurological disorder NOS
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 3
|
|
Nervous system disorders
Seizure
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 3
|
|
Nervous system disorders
Taste alteration
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Psychiatric disorders
Confusion
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Psychiatric disorders
Depression
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Psychiatric disorders
Personality change
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Psychiatric disorders
Psychosis
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
0.00%
0/107
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
25.0%
3/12 • Number of events 3
|
0.00%
0/3
|
2.8%
3/107 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Vascular disorders
Hypotension
|
0.00%
0/12
|
0.00%
0/3
|
3.7%
4/107 • Number of events 4
|
|
Vascular disorders
Thrombosis
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
15.0%
16/107 • Number of events 39
|
Other adverse events
| Measure |
Phase I, Dose Level 0
n=12 participants at risk
laboratory biomarker analysis: Correlative studies
|
Phase I, Dose Level 1
n=3 participants at risk
laboratory biomarker analysis: Correlative studies
|
Phase II
n=107 participants at risk
laboratory biomarker analysis: Correlative studies
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Blood disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 4
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
75.0%
9/12 • Number of events 28
|
33.3%
1/3 • Number of events 1
|
85.0%
91/107 • Number of events 704
|
|
Ear and labyrinth disorders
Ear disorder
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 7
|
|
Ear and labyrinth disorders
External ear pain
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Ear and labyrinth disorders
Hearing loss
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 16
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Eye disorders
Conjunctival disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Eye disorders
Dry eye syndrome
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Eye disorders
Eye disorder
|
0.00%
0/12
|
0.00%
0/3
|
3.7%
4/107 • Number of events 5
|
|
Eye disorders
Flashing vision
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Eye disorders
Vision blurred
|
0.00%
0/12
|
0.00%
0/3
|
6.5%
7/107 • Number of events 22
|
|
Eye disorders
Watering eyes
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 16
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/12
|
0.00%
0/3
|
12.1%
13/107 • Number of events 28
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/12
|
66.7%
2/3 • Number of events 2
|
37.4%
40/107 • Number of events 171
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
4/12 • Number of events 6
|
0.00%
0/3
|
34.6%
37/107 • Number of events 119
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/12
|
0.00%
0/3
|
10.3%
11/107 • Number of events 34
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/12
|
0.00%
0/3
|
7.5%
8/107 • Number of events 24
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 5
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 6
|
|
Gastrointestinal disorders
Fecal incontinence
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 5
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 2
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/12
|
0.00%
0/3
|
7.5%
8/107 • Number of events 13
|
|
Gastrointestinal disorders
Nausea
|
50.0%
6/12 • Number of events 25
|
33.3%
1/3 • Number of events 1
|
65.4%
70/107 • Number of events 386
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
41.7%
5/12 • Number of events 10
|
33.3%
1/3 • Number of events 1
|
35.5%
38/107 • Number of events 92
|
|
General disorders
Chills
|
0.00%
0/12
|
0.00%
0/3
|
4.7%
5/107 • Number of events 6
|
|
General disorders
Edema limbs
|
0.00%
0/12
|
0.00%
0/3
|
6.5%
7/107 • Number of events 13
|
|
General disorders
Fatigue
|
100.0%
12/12 • Number of events 53
|
66.7%
2/3 • Number of events 2
|
96.3%
103/107 • Number of events 942
|
|
General disorders
Fever
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
General disorders
Gait abnormal
|
0.00%
0/12
|
0.00%
0/3
|
7.5%
8/107 • Number of events 36
|
|
General disorders
Localized edema
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 4
|
|
Infections and infestations
Conjunctivitis infective
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
0.00%
0/107
|
|
Infections and infestations
Mucosal infection
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 7
|
|
Infections and infestations
Otitis media
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 2
|
|
Infections and infestations
Peripheral nerve infection
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Infections and infestations
Sinusitis
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 5
|
|
Infections and infestations
Upper aerodigestive tract infection
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/12
|
0.00%
0/3
|
3.7%
4/107 • Number of events 5
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Injury, poisoning and procedural complications
Bruising
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Injury, poisoning and procedural complications
Dermatitis radiation
|
16.7%
2/12 • Number of events 2
|
0.00%
0/3
|
8.4%
9/107 • Number of events 19
|
|
Injury, poisoning and procedural complications
Radiation recall reaction (dermatologic)
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Injury, poisoning and procedural complications
Vascular access complication
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 10
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
0.00%
0/107
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
4/12 • Number of events 4
|
66.7%
2/3 • Number of events 2
|
29.0%
31/107 • Number of events 69
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/12
|
0.00%
0/3
|
5.6%
6/107 • Number of events 7
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
23.4%
25/107 • Number of events 53
|
|
Investigations
Bilirubin increased
|
0.00%
0/12
|
0.00%
0/3
|
12.1%
13/107 • Number of events 51
|
|
Investigations
Creatinine increased
|
25.0%
3/12 • Number of events 12
|
0.00%
0/3
|
13.1%
14/107 • Number of events 56
|
|
Investigations
INR increased
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
0.93%
1/107 • Number of events 4
|
|
Investigations
Laboratory test abnormal
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
0.93%
1/107 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
75.0%
9/12 • Number of events 30
|
0.00%
0/3
|
60.7%
65/107 • Number of events 358
|
|
Investigations
Lymphocyte count decreased
|
58.3%
7/12 • Number of events 27
|
66.7%
2/3 • Number of events 2
|
47.7%
51/107 • Number of events 256
|
|
Investigations
Neutrophil count decreased
|
50.0%
6/12 • Number of events 14
|
0.00%
0/3
|
46.7%
50/107 • Number of events 198
|
|
Investigations
Platelet count decreased
|
66.7%
8/12 • Number of events 44
|
66.7%
2/3 • Number of events 2
|
85.0%
91/107 • Number of events 584
|
|
Investigations
Serum cholesterol increased
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Investigations
Weight gain
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 8
|
|
Investigations
Weight loss
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
15.9%
17/107 • Number of events 53
|
|
Metabolism and nutrition disorders
Anorexia
|
41.7%
5/12 • Number of events 17
|
66.7%
2/3 • Number of events 2
|
57.9%
62/107 • Number of events 274
|
|
Metabolism and nutrition disorders
Blood bicarbonate decreased
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 2
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
8.3%
1/12 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
13.1%
14/107 • Number of events 41
|
|
Metabolism and nutrition disorders
Dehydration
|
25.0%
3/12 • Number of events 3
|
33.3%
1/3 • Number of events 1
|
21.5%
23/107 • Number of events 32
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
4.7%
5/107 • Number of events 9
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
25.0%
3/12 • Number of events 6
|
33.3%
1/3 • Number of events 1
|
11.2%
12/107 • Number of events 20
|
|
Metabolism and nutrition disorders
Serum calcium increased
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 8
|
|
Metabolism and nutrition disorders
Serum magnesium decreased
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum magnesium increased
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum phosphate decreased
|
8.3%
1/12 • Number of events 4
|
33.3%
1/3 • Number of events 1
|
8.4%
9/107 • Number of events 15
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
8.3%
1/12 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
13.1%
14/107 • Number of events 26
|
|
Metabolism and nutrition disorders
Serum potassium increased
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
2.8%
3/107 • Number of events 4
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
33.3%
4/12 • Number of events 4
|
33.3%
1/3 • Number of events 1
|
12.1%
13/107 • Number of events 25
|
|
Metabolism and nutrition disorders
Serum sodium increased
|
0.00%
0/12
|
0.00%
0/3
|
3.7%
4/107 • Number of events 5
|
|
Metabolism and nutrition disorders
Serum triglycerides increased
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
0.00%
0/12
|
0.00%
0/3
|
8.4%
9/107 • Number of events 17
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness left-sided
|
0.00%
0/12
|
0.00%
0/3
|
3.7%
4/107 • Number of events 25
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/12
|
0.00%
0/3
|
7.5%
8/107 • Number of events 30
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
0.00%
0/12
|
0.00%
0/3
|
3.7%
4/107 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/12
|
0.00%
0/3
|
5.6%
6/107 • Number of events 19
|
|
Musculoskeletal and connective tissue disorders
Soft tissue necrosis upper limb
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Upper extremity dysfunction
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 6
|
|
Nervous system disorders
Acoustic nerve disorder NOS
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Nervous system disorders
Ataxia
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Nervous system disorders
Central nervous system necrosis
|
0.00%
0/12
|
0.00%
0/3
|
3.7%
4/107 • Number of events 16
|
|
Nervous system disorders
Cognitive disturbance
|
33.3%
4/12 • Number of events 11
|
0.00%
0/3
|
32.7%
35/107 • Number of events 194
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
0.00%
0/12
|
0.00%
0/3
|
6.5%
7/107 • Number of events 28
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
22.4%
24/107 • Number of events 86
|
|
Nervous system disorders
Intracranial hemorrhage
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Nervous system disorders
Memory impairment
|
50.0%
6/12 • Number of events 14
|
33.3%
1/3 • Number of events 1
|
41.1%
44/107 • Number of events 289
|
|
Nervous system disorders
Neurological disorder NOS
|
0.00%
0/12
|
0.00%
0/3
|
4.7%
5/107 • Number of events 33
|
|
Nervous system disorders
Oculomotor nerve disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 5
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/12
|
0.00%
0/3
|
6.5%
7/107 • Number of events 27
|
|
Nervous system disorders
Seizure
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
5.6%
6/107 • Number of events 6
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/12
|
0.00%
0/3
|
7.5%
8/107 • Number of events 28
|
|
Nervous system disorders
Taste alteration
|
50.0%
6/12 • Number of events 24
|
33.3%
1/3 • Number of events 1
|
49.5%
53/107 • Number of events 283
|
|
Nervous system disorders
Tremor
|
0.00%
0/12
|
0.00%
0/3
|
7.5%
8/107 • Number of events 20
|
|
Psychiatric disorders
Agitation
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
8.3%
1/12 • Number of events 1
|
0.00%
0/3
|
4.7%
5/107 • Number of events 6
|
|
Psychiatric disorders
Confusion
|
0.00%
0/12
|
0.00%
0/3
|
4.7%
5/107 • Number of events 9
|
|
Psychiatric disorders
Depression
|
0.00%
0/12
|
0.00%
0/3
|
7.5%
8/107 • Number of events 19
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/12
|
0.00%
0/3
|
15.9%
17/107 • Number of events 46
|
|
Psychiatric disorders
Personality change
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 5
|
|
Renal and urinary disorders
Cystitis
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Renal and urinary disorders
Hemorrhage urinary tract
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 2
|
|
Renal and urinary disorders
Protein urine positive
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 2
|
|
Renal and urinary disorders
Urinary frequency
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 4
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/12
|
0.00%
0/3
|
4.7%
5/107 • Number of events 11
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Renal and urinary disorders
Urogenital disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
0.00%
0/107
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
8.4%
9/107 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/12
|
0.00%
0/3
|
9.3%
10/107 • Number of events 15
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage nasal
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
41.7%
5/12 • Number of events 8
|
0.00%
0/3
|
30.8%
33/107 • Number of events 138
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 10
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hand-and-foot syndrome
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/12
|
0.00%
0/3
|
3.7%
4/107 • Number of events 16
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.00%
0/12
|
0.00%
0/3
|
1.9%
2/107 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Sweating
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Vascular disorders
Flushing
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Vascular disorders
Hematoma
|
0.00%
0/12
|
0.00%
0/3
|
0.93%
1/107 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.00%
0/12
|
0.00%
0/3
|
4.7%
5/107 • Number of events 29
|
|
Vascular disorders
Hypotension
|
0.00%
0/12
|
0.00%
0/3
|
2.8%
3/107 • Number of events 3
|
|
Vascular disorders
Thrombosis
|
0.00%
0/12
|
33.3%
1/3 • Number of events 1
|
4.7%
5/107 • Number of events 8
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60