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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00544284
First received: October 13, 2007
Last updated: February 14, 2013
Last verified: February 2013

October 13, 2007
February 14, 2013
January 2005
January 2012   (final data collection date for primary outcome measure)
Dose-limiting toxicity and maximum tolerated dose [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Dose-limiting toxicity and maximum tolerated dose
Complete list of historical versions of study NCT00544284 on ClinicalTrials.gov Archive Site
  • Pharmacokinetics [ Time Frame: Day 9 ] [ Designated as safety issue: No ]
  • Confirmed complete or partial response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Percentage of patients with 6-month progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics
  • Confirmed complete or partial response
  • Percentage of patients with 6-month progression-free survival
Not Provided
Not Provided
 
Bortezomib and Temozolomide in Treating Patients With Brain Tumors or Other Solid Tumors That Have Not Responded to Treatment
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.

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).

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Brain and Central Nervous System Tumors
  • Lymphoma
  • Metastatic Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Drug: bortezomib
  • Drug: temozolomide
  • Other: pharmacological study
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
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
January 2012
January 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00544284
04032, P30CA033572, CHNMC-04032, CDR0000570245
Not Provided
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Jana Portnow, MD Beckman Research Institute
City of Hope Medical Center
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP