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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00544284
• Other study ID #: 04032
• Secondary ID: P30CA033572CHNMC
• Status: Completed
• Phase: Phase 1
• First received: October 13, 2007
• Last updated: February 14, 2013
• Start date: January 2005
• Est. completion date: January 2012

Study information

• Verified date: February 2013
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• bortezomib

• temozolomide

Other:
• pharmacological study

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	City of Hope Medical Group	Pasadena	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity and maximum tolerated dose		28 days	Yes
Secondary	Pharmacokinetics		Day 9	No
Secondary	Confirmed complete or partial response		6 months	No
Secondary	Percentage of patients with 6-month progression-free survival		6 months	No