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Bortezomib and Temozolomide in Treating Patients With Brain Tumors or Other Solid Tumors That Have Not Responded to Treatment

Primary Purpose

Brain and Central Nervous System Tumors, Lymphoma, Metastatic Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bortezomib
temozolomide
pharmacological study
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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, tumors metastatic to brain, unspecified adult solid tumor, protocol specific, adult pilocytic astrocytoma, adult subependymal giant cell astrocytoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope Comprehensive Cancer Center
  • City of Hope Medical Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (temozolomide, bortezomib)

Arm Description

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).

Outcomes

Primary Outcome Measures

Dose-limiting toxicity and maximum tolerated dose

Secondary Outcome Measures

Pharmacokinetics
Confirmed complete or partial response
Percentage of patients with 6-month progression-free survival

Full Information

First Posted
October 13, 2007
Last Updated
February 14, 2013
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00544284
Brief Title
Bortezomib and Temozolomide in Treating Patients With Brain Tumors or Other Solid Tumors That Have Not Responded to Treatment
Official Title
A Phase I Study of Bortezomib and Temozolomide in Patients With Refractory Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors, Lymphoma, Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Keywords
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, tumors metastatic to brain, unspecified adult solid tumor, protocol specific, adult pilocytic astrocytoma, adult subependymal giant cell astrocytoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (temozolomide, bortezomib)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Type
Drug
Intervention Name(s)
temozolomide
Intervention Type
Other
Intervention Name(s)
pharmacological study
Primary Outcome Measure Information:
Title
Dose-limiting toxicity and maximum tolerated dose
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Pharmacokinetics
Time Frame
Day 9
Title
Confirmed complete or partial response
Time Frame
6 months
Title
Percentage of patients with 6-month progression-free survival
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jana Portnow, MD
Organizational Affiliation
City of Hope Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
City of Hope Medical Group
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21850464
Citation
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.
Results Reference
derived

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Bortezomib and Temozolomide in Treating Patients With Brain Tumors or Other Solid Tumors That Have Not Responded to Treatment

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