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| ID | Type | Description | Link |
|---|---|---|---|
| STU00008280 | Other Identifier | Northwestern University IRB |
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| Name | Class |
|---|---|
| Millennium Pharmaceuticals, Inc. | INDUSTRY |
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Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bortezomib together with temozolomide after surgery may kill any tumor cells that remain after surgery.
This phase II trial is studying how well giving bortezomib before surgery followed by giving bortezomib together with temozolomide after surgery works in treating patients with recurrent malignant glioma.
Patients receive bortezomib IV on days 1, 4, and 8. Patients then undergo surgical resection of the tumor on day 8 or 9.
Beginning approximately 14 days after surgery, patients receive oral temozolomide on days 1-7 and 14-21 and bortezomib IV on days 7 and 21. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Tumor tissue and blood samples are collected periodically for biomarker analysis, gene methylation studies, and pharmacokinetic studies.
After completion of study therapy, patients are followed up every 3 months for 2 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bortezomib + Temozolomide | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bortezomib | Drug | 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). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Surviving Without Disease Progression After 6 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). | From date of first treatment until disease progression, death, or early discontinuation of treatment (up to 24 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Achieving a Response to Treatment (Either Complete or Partial Response) as Defined by MacDonald Criteria | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of Expression of NFKBIA Gene With Response to Therapy and Survival. | The 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. | Tissue samples for analysis were obtained on the day of surgery for all patients |
Inclusion Criteria:
Histologically confirmed malignant glioma, including any of the following subtypes:
Must show unequivocal evidence of tumor recurrence or progression by MRI or CT scan with contrast
Candidate for surgery AND requires surgery
Failed prior standard radiotherapy and temozolomide
Life expectancy > 12 weeks
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Raizer, MD | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University | Chicago | Illinois | 60611 | United States |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pre-surgical Bortezomib |
|
| ||||||||||||||||||
| Surgical Resection |
| |||||||||||||||||||
| Post-sugery Bortezomib + Temozolomide |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Other Pre-specified | Correlation of Expression of NFKBIA Gene With Response to Therapy and Survival. | The 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. | Not Posted | Tissue samples for analysis were obtained on the day of surgery for all patients | ||||||||||||
| Primary | Number of Patients Surviving Without Disease Progression After 6 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). |
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Adverse events were assessed by exam, lab tests, and review with patients during study visits.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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, 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemoglobin decreased | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jeffrey Raizer, MD | Northwestern University | 312-503-4724 | jraizer@nmff.org |
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| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000069286 | Bortezomib |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
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|
| Temozolomide | Drug | After surgery, temozolomide is taken by mouth on days 1-7 and 14-21 of each cycle (1 cycle = 28 days). |
|
|
| Day of treatment post-surgery and then approximately every 8 weeks thereafter until off treatment |
| Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 3.0) | Adverse 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 | Days 1, 4, 8 pre-surgery, and then at the start of every cycle (approximately every 4 weeks) post-surgery while on treatment |
| Overall Survival (in Days) | 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-up |
| Overall Survival Rate at 6 Months | The rate of overall survival at 6 months (regardless of disease progression) was calculated. | After 6 months on study |
| Change in MGMT Methylation Status as Well as Other Methylation Patterns in Plasma | To determine MGMT methylation status as well as other methylation patterns in plasma | Blood samples drawn on days 1, 4, and 8 pre-surgery, and then prior to cycle 1 and every 2 cycles thereafter |
| Pharmacokinetics of Bortezomib in Tumor Tissue Taken at the Time of Surgery. | Tissue sample taken at the time of surgery for all patients. |
|
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Posted |
| Number |
| participants |
| From date of first treatment until disease progression, death, or early discontinuation of treatment (up to 24 months) |
|
|
|
| Secondary | Number of Participants Achieving a Response to Treatment (Either Complete or Partial Response) as Defined by MacDonald Criteria | 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). | Only those participants who had residual tumor remaining after surgical resection were evaluated for this outcome. | Posted | Number | participants | Day of treatment post-surgery and then approximately every 8 weeks thereafter until off treatment |
|
|
|
| Secondary | Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 3.0) | Adverse 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 | Posted | Number | adverse events | Days 1, 4, 8 pre-surgery, and then at the start of every cycle (approximately every 4 weeks) post-surgery while on treatment |
|
|
|
| Other Pre-specified | Change in MGMT Methylation Status as Well as Other Methylation Patterns in Plasma | To determine MGMT methylation status as well as other methylation patterns in plasma | Not Posted | Blood samples drawn on days 1, 4, and 8 pre-surgery, and then prior to cycle 1 and every 2 cycles thereafter |
| Other Pre-specified | Pharmacokinetics of Bortezomib in Tumor Tissue Taken at the Time of Surgery. | Not Posted | Tissue sample taken at the time of surgery for all patients. |
| Secondary | Overall Survival (in Days) | Posted | Median | 95% Confidence Interval | days | 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-up |
|
|
|
| Secondary | Overall Survival Rate at 6 Months | The rate of overall survival at 6 months (regardless of disease progression) was calculated. | The 6-month overall survival rate was based on a median of 168 days of follow-up. | Posted | Number | percentage of participants | After 6 months on study |
|
|
|
| 3 |
| 10 |
| 10 |
| 10 |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage, CNS | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Leukocytes decreased | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cardiac General - Other | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| INR elevated | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue (asthenia, lethargy, malaise) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Injection site reaction/extravasation changes | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis/stomatitis -oral cavity | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection with unknown ANC - wound | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection - Other | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| ALT, SGPT elevated | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| AST, SGOT elevated | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Albumin, serum-low (hypoalbuminemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Alkaline phosphatase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Calcium, serum-low (hypocalcemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Magnesium, serum-low (hypomagnesemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Phosphate, serum-low (hypophosphatemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Potassium, serum-low (hypokalemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: motor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: sensory | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Seizure | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Syncope (fainting) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ataxia (incoordination) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Cognitive disturbance | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mood alteration - Anxiety | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mood alteration - Depression | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial - CN II Vision | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial - CN VII Motor-face; Sensory-taste | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial - CN XI Motor-sternomastoid and trapezius | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vision-blurred vision | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Head/headache | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Muscle | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D001896 |
| Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D007093 | Imidazoles |
| D001393 | Azoles |
| Title | Measurements |
|---|
|
| Grade 4 |
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| Grade 5 |
|