Trial Outcomes & Findings for Presurgery Bortezomib for Recurrent Malignant Gliomas Followed by Postop Bortezomib & Temozolomide (NCT NCT00990652)
NCT ID: NCT00990652
Last Updated: 2014-01-13
Results Overview
Patients will be monitored from date of first treatment to the date of first observation of progressive disease, non-reversible neurologic progression or increasing steroid requirements, death due to any cause, or early discontinuation of treatment. Progression-free survival will be defined as the absence of any of the above after 6 months. Progression (defined by MacDonald Criteria) is a 25% increase in the sum of products of all measurable lesions over smallest sum observed compared to baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to the cancer).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
10 participants
Primary outcome timeframe
From date of first treatment until disease progression, death, or early discontinuation of treatment (up to 24 months)
Results posted on
2014-01-13
Participant Flow
The study opened on May 21, 2009 with an accrual goal of 29 patients; the study was designed to enroll 10 patients initially and do an interim efficacy assessment. Accrual was suspended on February 11, 2011 for this analysis. The interim results did not support further accrual, and so the study was permanently closed to accrual on March 29, 2011.
Participant milestones
| Measure |
Bortezomib + Temozolomide
Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery (approximately 14 days later), patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 4 weeks or 28 days). Temozolomide (75 mg/m\^2) is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib (1.3 mg/m\^2) is given intravenously (IV) on days 7 and 21 of each cycle. Patients continue to receive cycles of treatment until disease progression, development of unacceptable toxicity, or up to a maximum of 24 months.
|
|---|---|
|
Pre-surgical Bortezomib
STARTED
|
10
|
|
Pre-surgical Bortezomib
COMPLETED
|
9
|
|
Pre-surgical Bortezomib
NOT COMPLETED
|
1
|
|
Surgical Resection
STARTED
|
9
|
|
Surgical Resection
COMPLETED
|
9
|
|
Surgical Resection
NOT COMPLETED
|
0
|
|
Post-sugery Bortezomib + Temozolomide
STARTED
|
9
|
|
Post-sugery Bortezomib + Temozolomide
COMPLETED
|
8
|
|
Post-sugery Bortezomib + Temozolomide
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Bortezomib + Temozolomide
Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery (approximately 14 days later), patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 4 weeks or 28 days). Temozolomide (75 mg/m\^2) is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib (1.3 mg/m\^2) is given intravenously (IV) on days 7 and 21 of each cycle. Patients continue to receive cycles of treatment until disease progression, development of unacceptable toxicity, or up to a maximum of 24 months.
|
|---|---|
|
Pre-surgical Bortezomib
Adverse Event
|
1
|
|
Post-sugery Bortezomib + Temozolomide
Withdrawal by Subject
|
1
|
Baseline Characteristics
Presurgery Bortezomib for Recurrent Malignant Gliomas Followed by Postop Bortezomib & Temozolomide
Baseline characteristics by cohort
| Measure |
Bortezomib + Temozolomide
n=10 Participants
Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery (approximately 14 days later), patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 4 weeks or 28 days). Temozolomide (75 mg/m\^2) is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib (1.3 mg/m\^2) is given intravenously (IV) on days 7 and 21 of each cycle. Patients continue to receive cycles of treatment until disease progression, development of unacceptable toxicity, or up to a maximum of 24 months.
|
|---|---|
|
Age, Customized
21-30 years
|
0 participants
n=5 Participants
|
|
Age, Customized
31-40 years
|
0 participants
n=5 Participants
|
|
Age, Customized
41-50 years
|
6 participants
n=5 Participants
|
|
Age, Customized
51-60 years
|
2 participants
n=5 Participants
|
|
Age, Customized
61-70 years
|
2 participants
n=5 Participants
|
|
Age, Customized
71-80 years
|
0 participants
n=5 Participants
|
|
Age, Customized
81-90 years
|
0 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From date of first treatment until disease progression, death, or early discontinuation of treatment (up to 24 months)Patients will be monitored from date of first treatment to the date of first observation of progressive disease, non-reversible neurologic progression or increasing steroid requirements, death due to any cause, or early discontinuation of treatment. Progression-free survival will be defined as the absence of any of the above after 6 months. Progression (defined by MacDonald Criteria) is a 25% increase in the sum of products of all measurable lesions over smallest sum observed compared to baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to the cancer).
Outcome measures
| Measure |
Bortezomib + Temozolomide
n=10 Participants
Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery (approximately 14 days later), patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 4 weeks or 28 days). Temozolomide (75 mg/m\^2) is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib (1.3 mg/m\^2) is given intravenously (IV) on days 7 and 21 of each cycle. Patients continue to receive cycles of treatment until disease progression, development of unacceptable toxicity, or up to a maximum of 24 months.
|
|---|---|
|
Number of Patients Surviving Without Disease Progression After 6 Months
|
0 participants
|
SECONDARY outcome
Timeframe: Day of treatment post-surgery and then approximately every 8 weeks thereafter until off treatmentPopulation: Only those participants who had residual tumor remaining after surgical resection were evaluated for this outcome.
This measure was assessed only in patients who had residual tumor post-operatively. Per MacDonald Criteria: Complete Response requires complete disappearance of all measurable \& evaluable disease, no new lesions, no evidence of non-evaluable disease, and only minimal or no use of steroids. Partial Response is defined as \>= 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions, no progression of evaluable disease, and no new lesions. Responders must be on the same or decreasing doses of steroid. Response was assessed by imaging (MRI or CT with contrast).
Outcome measures
| Measure |
Bortezomib + Temozolomide
n=3 Participants
Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery (approximately 14 days later), patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 4 weeks or 28 days). Temozolomide (75 mg/m\^2) is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib (1.3 mg/m\^2) is given intravenously (IV) on days 7 and 21 of each cycle. Patients continue to receive cycles of treatment until disease progression, development of unacceptable toxicity, or up to a maximum of 24 months.
|
|---|---|
|
Number of Participants Achieving a Response to Treatment (Either Complete or Partial Response) as Defined by MacDonald Criteria
|
0 participants
|
SECONDARY outcome
Timeframe: Days 1, 4, 8 pre-surgery, and then at the start of every cycle (approximately every 4 weeks) post-surgery while on treatmentAdverse events (AEs) were graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0. In general, AEs are graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Outcome measures
| Measure |
Bortezomib + Temozolomide
n=10 Participants
Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery (approximately 14 days later), patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 4 weeks or 28 days). Temozolomide (75 mg/m\^2) is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib (1.3 mg/m\^2) is given intravenously (IV) on days 7 and 21 of each cycle. Patients continue to receive cycles of treatment until disease progression, development of unacceptable toxicity, or up to a maximum of 24 months.
|
|---|---|
|
Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 3.0)
Grade 5
|
0 adverse events
|
|
Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 3.0)
Grade 1
|
80 adverse events
|
|
Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 3.0)
Grade 2
|
30 adverse events
|
|
Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 3.0)
Grade 3
|
11 adverse events
|
|
Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 3.0)
Grade 4
|
1 adverse events
|
SECONDARY outcome
Timeframe: Days 1, 4, 8 pre-surgery, once per cycle (every 4 weeks) while on treatment post-surgery, and then every 3 months up to 2 years during follow-upOutcome measures
| Measure |
Bortezomib + Temozolomide
n=10 Participants
Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery (approximately 14 days later), patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 4 weeks or 28 days). Temozolomide (75 mg/m\^2) is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib (1.3 mg/m\^2) is given intravenously (IV) on days 7 and 21 of each cycle. Patients continue to receive cycles of treatment until disease progression, development of unacceptable toxicity, or up to a maximum of 24 months.
|
|---|---|
|
Overall Survival (in Days)
|
248 days
Interval 122.0 to 397.0
|
SECONDARY outcome
Timeframe: After 6 months on studyPopulation: The 6-month overall survival rate was based on a median of 168 days of follow-up.
The rate of overall survival at 6 months (regardless of disease progression) was calculated.
Outcome measures
| Measure |
Bortezomib + Temozolomide
n=10 Participants
Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery (approximately 14 days later), patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 4 weeks or 28 days). Temozolomide (75 mg/m\^2) is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib (1.3 mg/m\^2) is given intravenously (IV) on days 7 and 21 of each cycle. Patients continue to receive cycles of treatment until disease progression, development of unacceptable toxicity, or up to a maximum of 24 months.
|
|---|---|
|
Overall Survival Rate at 6 Months
|
69 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Tissue samples for analysis were obtained on the day of surgery for all patientsThe effects of bortezomib on the endogenous modulators of NF-Kappa B pathways, especially the NFKBIA gene (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) were assessed using novel assay technology; expression of NFKBIA was then correlated with response to therapy and patient survival.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Blood samples drawn on days 1, 4, and 8 pre-surgery, and then prior to cycle 1 and every 2 cycles thereafterTo determine MGMT methylation status as well as other methylation patterns in plasma
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Tissue sample taken at the time of surgery for all patients.Outcome measures
Outcome data not reported
Adverse Events
Bortezomib + Temozolomide
Serious events: 3 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bortezomib + Temozolomide
n=10 participants at risk
Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery, patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 28 days). Temozolomide is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib injections are given on days 7 and 21 of each cycle.
Bortezomib: Before surgery, an injection of bortezomib is given on days 1, 4, and 8. After surgery, bortezomib is given on days 7 and 21 of each cycle (1 cycle = 28 days).
Temozolomide: After surgery, temozolomide is taken by mouth on days 1-7 and 14-21 of each cycle (1 cycle = 28 days).
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Hemorrhage, CNS
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Infections and infestations
Infection with normal ANC
|
14.3%
1/7 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
Other adverse events
| Measure |
Bortezomib + Temozolomide
n=10 participants at risk
Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery, patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 28 days). Temozolomide is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib injections are given on days 7 and 21 of each cycle.
Bortezomib: Before surgery, an injection of bortezomib is given on days 1, 4, and 8. After surgery, bortezomib is given on days 7 and 21 of each cycle (1 cycle = 28 days).
Temozolomide: After surgery, temozolomide is taken by mouth on days 1-7 and 14-21 of each cycle (1 cycle = 28 days).
|
|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
60.0%
6/10 • Number of events 6
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Blood and lymphatic system disorders
Leukocytes decreased
|
20.0%
2/10 • Number of events 2
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
40.0%
4/10 • Number of events 4
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Blood and lymphatic system disorders
Platelets
|
50.0%
5/10 • Number of events 5
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Cardiac disorders
Cardiac General - Other
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Cardiac disorders
Hypertension
|
20.0%
2/10 • Number of events 2
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Blood and lymphatic system disorders
INR elevated
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
60.0%
6/10 • Number of events 6
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Skin and subcutaneous tissue disorders
Injection site reaction/extravasation changes
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Gastrointestinal disorders
Constipation
|
20.0%
2/10 • Number of events 2
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Gastrointestinal disorders
Mucositis/stomatitis -oral cavity
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Gastrointestinal disorders
Nausea
|
30.0%
3/10 • Number of events 3
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Infections and infestations
Infection with unknown ANC - wound
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Infections and infestations
Infection - Other
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Metabolism and nutrition disorders
ALT, SGPT elevated
|
60.0%
6/10 • Number of events 6
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Metabolism and nutrition disorders
AST, SGOT elevated
|
40.0%
4/10 • Number of events 4
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
40.0%
4/10 • Number of events 4
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Metabolism and nutrition disorders
Alkaline phosphatase
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
40.0%
4/10 • Number of events 4
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
60.0%
6/10 • Number of events 6
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Metabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)
|
30.0%
3/10 • Number of events 3
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
20.0%
2/10 • Number of events 2
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
20.0%
2/10 • Number of events 2
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Neuropathy: motor
|
30.0%
3/10 • Number of events 3
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Neuropathy: sensory
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Seizure
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Syncope (fainting)
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Ataxia (incoordination)
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Cognitive disturbance
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Dizziness
|
40.0%
4/10 • Number of events 4
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Memory impairment
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Mood alteration - Anxiety
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Mood alteration - Depression
|
20.0%
2/10 • Number of events 2
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Neuropathy: cranial - CN II Vision
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Neuropathy: cranial - CN VII Motor-face; Sensory-taste
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Nervous system disorders
Neuropathy: cranial - CN XI Motor-sternomastoid and trapezius
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Ear and labyrinth disorders
Vision-blurred vision
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
General disorders
Pain - Head/headache
|
50.0%
5/10 • Number of events 5
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
|
Musculoskeletal and connective tissue disorders
Pain - Muscle
|
10.0%
1/10 • Number of events 1
Adverse events were assessed by exam, lab tests, and review with patients during study visits.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place