Clinical trial NCT00544284: Bortezomib and Temozolomide in Treating Patients With Brain Tumors or Other Solid Tumors That Have Not Responded to Treatment
Official title: A Phase I Study of Bortezomib and Temozolomide in Patients With Refractory Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Lymphoma
Metastatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: adult glioblastoma
adult anaplastic astrocytoma
adult giant cell glioblastoma
recurrent adult brain tumor
adult gliosarcoma
adult mixed glioma
adult anaplastic oligodendroglioma
primary central nervous system lymphoma
adult diffuse astrocytoma
adult brain stem glioma
adult central nervous system germ cell tumor
adult choroid plexus tumor
adult craniopharyngioma
adult ependymoblastoma
adult medulloblastoma
adult supratentorial primitive neuroectodermal tumor (PNET)
adult anaplastic ependymoma
adult ependymoma
adult myxopapillary ependymoma
adult subependymoma
adult anaplastic meningioma
adult melanocytic lesion
adult meningeal hemangiopericytoma
adult grade I meningioma
adult grade II meningioma
adult grade III meningioma
adult papillary meningioma
adult oligodendroglioma
adult pineoblastoma
adult pineocytoma
tumors metastatic to brain
unspecified adult solid tumor, protocol specific
adult pilocytic astrocytoma
adult subependymal giant cell astrocytoma
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-10-16
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: Dose-limiting toxicity and maximum tolerated dose
timeFrame: 28 days
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: Day 9
measure: Confirmed complete or partial response
timeFrame: 6 months
measure: Percentage of patients with 6-month progression-free survival
timeFrame: 6 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Pasadena
country: United States
facility: City of Hope Medical Group
state: California
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Jana Portnow, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.