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

NCT ID: NCT00544284

Last Updated: 2013-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2012-01-31

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).

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

temozolomide

Intervention Type: DRUG

pharmacological study

Intervention Type: OTHER

Interventions

bortezomib

Intervention Type: DRUG

temozolomide

Intervention Type: DRUG

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

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

• 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

• 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:

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jana Portnow, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

City of Hope Medical Group

Pasadena, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 21850464 (View on PubMed)

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-04032

Identifier Type: -

Identifier Source: secondary_id

CDR0000570245

Identifier Type: REGISTRY

Identifier Source: secondary_id

04032

Identifier Type: -

Identifier Source: org_study_id