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A Phase I Study of Bortezomib and Temozolomide in Patients With Refractory Solid Tumors

Phase 1
18 Years
Not Enrolling
Brain and Central Nervous System Tumors, Lymphoma, Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of Bortezomib and Temozolomide in Patients With Refractory Solid Tumors



- 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.


- 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).

Inclusion Criteria


- 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


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

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


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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity and maximum tolerated dose

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Jana Portnow, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Federal Government

Study ID:




Start Date:

January 2005

Completion Date:

January 2012

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Lymphoma
  • Metastatic Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
  • Brain Neoplasms
  • Lymphoma
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



City of Hope Comprehensive Cancer Center Duarte, California  91010
City of Hope Medical Group Pasadena, California  91105