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

February 14, 2013 updated by: City of Hope Medical Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / 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).

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope Comprehensive Cancer Center
      • Pasadena, California, United States, 91105
        • City of Hope Medical Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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).
Other: pharmacological study
Drug: temozolomide
Drug: bortezomib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose-limiting toxicity and maximum tolerated dose
Time Frame: 28 days
28 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics
Time Frame: Day 9
Day 9
Confirmed complete or partial response
Time Frame: 6 months
6 months
Percentage of patients with 6-month progression-free survival
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

October 13, 2007

First Submitted That Met QC Criteria

October 13, 2007

First Posted (Estimate)

October 16, 2007

Study Record Updates

Last Update Posted (Estimate)

February 15, 2013

Last Update Submitted That Met QC Criteria

February 14, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 04032
  • P30CA033572 (U.S. NIH Grant/Contract)
  • CHNMC-04032
  • CDR0000570245 (Registry Identifier: NCI PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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