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:
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
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 28, 2014