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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00544284
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

City of Hope Medical Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jana Portnow, MD
Principal Investigator Affiliation City of Hope Comprehensive Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain and Central Nervous System Tumors, Lymphoma, Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Additional Details

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).

Arms & Interventions

Arms

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).

Interventions

Drug: - bortezomib

Drug: - temozolomide

Other: - pharmacological study

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

City of Hope Comprehensive Cancer Center, Duarte, California

Status

Address

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000

City of Hope Medical Group, Pasadena, California

Status

Address

City of Hope Medical Group

Pasadena, California, 91105