Bortezomib and Temozolomide in Treating Patients With Brain Tumors or Other Solid Tumors That Have Not Responded to Treatment
This study has been completed.
Sponsor:
City of Hope Medical Center
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00544284
First received: October 13, 2007
Last updated: February 14, 2013
Last verified: February 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors Lymphoma Metastatic Cancer Unspecified Adult Solid Tumor, Protocol Specific |
Drug: bortezomib Drug: temozolomide Other: pharmacological study |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I Study of Bortezomib and Temozolomide in Patients With Refractory Solid Tumors |
Resource links provided by NLM:
Further study details as provided by City of Hope Medical Center:
Primary Outcome Measures:
- Dose-limiting toxicity and maximum tolerated dose [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Pharmacokinetics [ Time Frame: Day 9 ] [ Designated as safety issue: No ]
- Confirmed complete or partial response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Percentage of patients with 6-month progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
| Enrollment: | 25 |
| Study Start Date: | January 2005 |
| Study Completion Date: | January 2012 |
| Primary Completion Date: | January 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (temozolomide, bortezomib)
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).
|
Drug: bortezomib Drug: temozolomide Other: pharmacological study |
Detailed Description:
OBJECTIVES:
Primary
- To determine the dose-limiting toxicities and maximum tolerated doses of bortezomib and temozolomide in patients with recurrent high-grade gliomas, recurrent metastatic brain tumors, or other refractory solid tumors.
Secondary
- To evaluate the pharmacokinetics of bortezomib in patients taking hepatic enzyme-inducing anticonvulsants (Group A) and in those who are not (Group B).
- To describe the proportion of study patients treated with bortezomib and temozolomide who obtain a confirmed complete response or partial response.
- To report the percentage of patients with 6-month progression-free survival.
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).
- 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).
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed solid tumors including the following
- Recurrent high-grade glioma
- Recurrent metastatic brain tumors
- Recurrent primary brain tumor including primary CNS lymphoma
- Other refractory solid tumors
- 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:
- Karnofsky performance status 60-100%
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
- Total bilirubin ≤ 2.0 mg/dL
- AST ≤ 4.0 x ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Patient must be able to understand and is willing to sign a written informed consent document
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
- Any ECG abnormalities prior to study entry must be documented by the investigator as not medically relevant
- 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
- Corticosteroids for cerebral edema allowed provided the patient is on a stable dose for at least 1 week
Exclusion criteria:
- Patients enrolled on another clinical trial
- HIV-positive patients on antiretroviral therapy
- Concurrent chemotherapy or radiotherapy
- Patient requires anti-seizure medication but is not on a stable dose and agent of anti-seizure medication
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00544284
Locations
| United States, California | |
| City of Hope Comprehensive Cancer Center | |
| Duarte, California, United States, 91010-3000 | |
| City of Hope Medical Group | |
| Pasadena, California, United States, 91105 | |
Sponsors and Collaborators
City of Hope Medical Center
Investigators
| Principal Investigator: | Jana Portnow, MD | Beckman Research Institute |
More Information
Additional Information:
No publications provided by City of Hope Medical Center
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | City of Hope Medical Center |
| ClinicalTrials.gov Identifier: | NCT00544284 History of Changes |
| Other Study ID Numbers: | 04032, P30CA033572, CHNMC-04032, CDR0000570245 |
| Study First Received: | October 13, 2007 |
| Last Updated: | February 14, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by City of Hope Medical Center:
|
adult glioblastoma adult anaplastic astrocytoma adult giant cell glioblastoma recurrent adult brain tumor adult gliosarcoma adult mixed glioma adult anaplastic oligodendroglioma primary central nervous system lymphoma adult diffuse astrocytoma adult brain stem glioma adult central nervous system germ cell tumor adult choroid plexus tumor adult craniopharyngioma adult ependymoblastoma adult medulloblastoma |
adult supratentorial primitive neuroectodermal tumor (PNET) adult anaplastic ependymoma adult ependymoma adult myxopapillary ependymoma adult subependymoma adult anaplastic meningioma adult melanocytic lesion adult meningeal hemangiopericytoma adult grade I meningioma adult grade II meningioma adult grade III meningioma adult papillary meningioma adult oligodendroglioma adult pineoblastoma adult pineocytoma |
Additional relevant MeSH terms:
|
Brain Neoplasms Lymphoma Neoplasm Metastasis Neoplasms Neoplasms, Second Primary Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders |
Immune System Diseases Neoplastic Processes Pathologic Processes Temozolomide Dacarbazine Bortezomib Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Protease Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 19, 2013