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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA033572 | U.S. NIH Grant/Contract | View source | |
| CHNMC-04032 | |||
| CDR0000570245 | Registry Identifier | NCI PDQ |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. 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 together with temozolomide may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with temozolomide in treating patients with brain tumors or other solid tumors that have not responded to treatment.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients are stratified according to concurrent hepatic enzyme-inducing anticonvulsants (HEIAs) (Group A) versus concurrent anticonvulsant drugs that cause modest or no induction of hepatic metabolic enzymes OR no anticonvulsant drugs (Group B).
All patients undergo blood sample collection periodically for pharmacokinetic studies. Samples are analyzed for bortezomib concentration (groups A and B) and trough levels of anticonvulsants (group A only).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (temozolomide, bortezomib) | Experimental | GROUP A: Patients receive oral temozolomide once a day on days 1-5 and bortezomib IV on days 2, 5, 9, and 12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP B: Patients receive temozolomide and bortezomib as in group A. Cohorts of patients in both groups receive escalating doses of both study drugs until the maximum tolerated doses are determined. All patients undergo blood sample collection periodically for pharmacokinetic studies. Samples are analyzed for bortezomib concentration (groups A and B) and trough levels of anticonvulsants (group A only). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| bortezomib | Drug |
| ||
| temozolomide |
| Measure | Description | Time Frame |
|---|---|---|
| Dose-limiting toxicity and maximum tolerated dose | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics | Day 9 | |
| Confirmed complete or partial response | 6 months | |
| Percentage of patients with 6-month progression-free survival |
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DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed solid tumors including the following
Unresectable disease for which standard curative or palliative measures do not exist or are no longer effective
Measurable or nonmeasurable disease
PATIENT CHARACTERISTICS:
Inclusion criteria:
Exclusion criteria:
Any of the following conditions:
Myocardial infarction within the past 6 months or New York Heart Association class III or IV heart failure
Uncontrolled angina
Severe uncontrolled ventricular arrhythmias
ECG evidence of acute ischemia or active conduction system abnormalities
Serious medical or psychiatric illness that would, in the opinion of the investigator, potentially interfere with the completion of treatment
History of sensitivity to boron or mannitol
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
At least 4 weeks since prior chemotherapy (6 weeks for nitrosourea-containing chemotherapy), immunotherapy, or radiotherapy and recovered
More than 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes for patients in group A
Recovered from major surgery
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jana Portnow, MD | City of Hope Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope Comprehensive Cancer Center | Duarte | California | 91010-3000 | United States | ||
| City of Hope Medical Group |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21850464 | Derived | Portnow J, Frankel P, Koehler S, Twardowski P, Shibata S, Martel C, Morgan R, Cristea M, Chow W, Lim D, Chung V, Reckamp K, Leong L, Synold TW. A phase I study of bortezomib and temozolomide in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2012 Feb;69(2):505-14. doi: 10.1007/s00280-011-1721-x. Epub 2011 Aug 18. |
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|
| pharmacological study | Other |
|
| 6 months |
| Pasadena |
| California |
| 91105 |
| United States |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D008223 | Lymphoma |
| D009362 | Neoplasm Metastasis |
| D005909 | Glioblastoma |
| D001254 | Astrocytoma |
| D001932 | Brain Neoplasms |
| D018316 | Gliosarcoma |
| D005910 | Glioma |
| D009837 | Oligodendroglioma |
| D016545 | Choroid Plexus Neoplasms |
| D003397 | Craniopharyngioma |
| D018242 | Neuroectodermal Tumors, Primitive |
| D008527 | Medulloblastoma |
| D004806 | Ependymoma |
| D018315 | Glioma, Subependymal |
| D008579 | Meningioma |
| D010871 | Pinealoma |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D002551 | Cerebral Ventricle Neoplasms |
| D009383 | Neoplasms, Vascular Tissue |
| D008577 | Meningeal Neoplasms |
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| ID | Term |
|---|---|
| D000069286 | Bortezomib |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D007093 | Imidazoles |
| D001393 | Azoles |
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