Temsirolimus With or Without Temozolomide in Treating Patients With Primary or Metastatic Brain Tumors - Full Text View

Sponsors and Collaborators:	Beckman Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00784914

Purpose

RATIONALE: Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Studying samples of blood and tumor tissue from patients with cancer in the laboratory may help doctors learn more about how this treatment is used by the body.

PURPOSE: This phase I trial is studying the best dose of temsirolimus given with or without temozolomide in treating patients with primary or metastatic brain tumors.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: temozolomide Drug: temsirolimus Procedure: observation	Phase I

MedlinePlus related topics: Brain Cancer Cancer

Drug Information available for: Temozolomide CCI 779

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Dose Escalation Study Using Intracerebral Microdialysis to Assess the Neuropharmacokinetics and Neuropharmacodynamics of Temsirolimus With and Without Temozolomide in Patients With Primary or Metastatic Brain Tumors

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Feasibility of using a microdialysis catheter to assess the neuropharmacodynamics (nPD) of temsirolimus with and without temozolomide [ Designated as safety issue: No ]
Changes in intracerebral levels of vascular endothelial growth factor (VEGF), interleukin-1ß (IL-1ß), and other cytokines [ Designated as safety issue: No ]

Secondary Outcome Measures:

Relationship between temsirolimus dose and changes in intracerebral levels of VEGF, IL-1ß, and other cytokines [ Designated as safety issue: No ]
Affect of temozolomide on the nPD of temsirolimus when the two agents are given concurrently versus temsirolimus alone [ Designated as safety issue: No ]
Relationship between the degree of microvascular proliferation and the tensin homologue deleted on chromosome 10 (PTEN) status in tumor tissue [ Designated as safety issue: No ]
Relationship between changes in intracerebral cytokine levels after treatment with temsirolimus [ Designated as safety issue: No ]

Estimated Enrollment:	15
Study Start Date:	June 2008
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Cohort 1: No Intervention Patients do not receive temsirolimus or temozolomide.	Procedure: observation Patients do not receive temsirolimus or temozolomide
Cohorts 2-4: Experimental Beginning 24 hours after surgery, patients receive 1 dose of temsirolimus IV over 30 minutes.	Drug: temsirolimus Receive temsirolimus IV
Cohort 5: Experimental Beginning 24 hours after surgery, patients receive 1 dose of temsirolimus IV over 30 minutes and 1 dose of oral temozolomide.	Drug: temozolomide Received oral temozolomide Drug: temsirolimus Receive temsirolimus IV

Detailed Description:

OBJECTIVES:

Primary

Determine the feasibility of using a microdialysis catheter with a high cut-off membrane to perform neuropharmacodynamics (nPD) assessment of targeted therapy with a mammalian target of rapamycin (mTOR) inhibitor, where nPD is defined as changes in intracerebral levels of vascular endothelial growth factor (VEGF), interleukin-1ß (IL-1ß), and other cytokines.

Secondary

Assess the relationship between temsirolimus dose and changes in intracerebral levels of VEGF, IL-1ß, and other cytokines.
Evaluate whether the nPD of temsirolimus is affected by temozolomide, when the two agents are given concurrently versus temsirolimus alone.
Assess the relationship between the degree of microvascular proliferation and the tensin homologue deleted on chromosome 10 (PTEN) status in tumor tissue.
Assess the relationship between changes in intracerebral cytokine levels after treatment with temsirolimus.

OUTLINE: This is a dose-escalation study of temsirolimus. All patients undergo debulking craniotomy or stereotactic biopsy and a placement of a intracerebral CMA 71 microdialysis (ICMD) catheter. Patients then are assigned to 1 of 5 treatment cohorts.

Cohort 1: Patients do not receive temsirolimus or temozolomide.
Cohorts 2-4 (dose escalating cohorts):Beginning 24 hours after surgery, patients receive 1 dose of temsirolimus IV over 30 minutes.
Cohort 5: Beginning 24 hours after surgery, patients receive established dose of temsirolimus IV over 30 minutes (once) and 1 dose of oral temozolomide.

Blood samples from cohorts 2-5 are collected periodically prior to and after study therapy for pharmacokinetic studies. Dialysate samples from all patients are continuously collected for 72 hours to determine changes in cytokine levels and brain biochemistry. Tumor tissue samples are collected during surgery and are assessed for the presence of microvascular proliferation and necrosis by immunohistochemical staining.

After completion of study therapy and removal of ICMD catheter, patients are followed for 30 days.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of a primary or metastatic brain tumor
Requires a surgical debulking or a stereotactic biopsy for the purpose of diagnosis or differentiating between tumor progression and treatment-induced effects following radiation therapy and/or chemotherapy

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 60-100% OR ECOG/Zubrod PS 0-2
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Total bilirubin ≤ 2.0 mg/dL
AST ≤ 4 times upper limit of normal (ULN)
Serum creatinine ≤ 1.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No coagulopathy, increased susceptibility to infection, or bleeding disorders
No serious medical or psychiatric illness that could, in the investigator's opinion, potentially preclude the completion of treatment protocol
No contraindication to treatment with temsirolimus and temozolomide (cohort 5)
No allergy to temsirolimus, sirolimus (rapamycin), temozolomide, or dextran

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No concurrent hepatic enzyme-induced anticonvulsants, including any of the following:
- Phenytoin
- Carbamazepine
- Phenobarbital
- Primidone
- Oxcarbazepine
Recovered from any toxicity of any prior therapy
Not planning to receive radiotherapy, other chemotherapy, or to participate in another clinical trial from the time of surgery until microdialysis catheter is removed
No concurrent anticoagulant therapy
No concurrent antiretroviral therapy for HIV-positive patients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00784914

Locations

United States, California
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Jana Portnow, MD 800-826-4673

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Jana Portnow, MD

Beckman Research Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	City of Hope Comprehensive Cancer Center ( Jana Portnow )
Study ID Numbers:	CDR0000617019, CHNMC-07064
Study First Received:	November 1, 2008
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00784914
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult pineocytoma
adult anaplastic astrocytoma
adult diffuse astrocytoma
adult craniopharyngioma
adult choroid plexus tumor
adult brain stem glioma
adult tumors metastatic to brain
recurrent adult brain tumor
adult gliosarcoma
adult giant cell glioblastoma
adult ependymoblastoma
adult medulloblastoma
adult supratentorial primitive neuroectodermal tumor (PNET)

adult anaplastic ependymoma
adult ependymoma
adult myxopapillary ependymoma
adult subependymoma
adult mixed glioma
adult melanocytic lesion
adult meningeal hemangiopericytoma
adult grade I meningioma
adult grade II meningioma
adult grade III meningioma
adult anaplastic oligodendroglioma
adult oligodendroglioma
adult pineoblastoma

Study placed in the following topic categories:

Choroid Plexus Neoplasms
Glioblastoma
Neuroectodermal Tumors, Primitive
Astrocytoma
Central Nervous System Diseases
Central Nervous System Neoplasms
Brain Diseases
Temozolomide
Hemangiopericytoma
Recurrence
Ependymoma
Brain Neoplasms

Neuroectodermal Tumors
Craniopharyngioma
Medulloblastoma
Neuroepithelioma
Oligodendroglioma
Meningioma
Glioma
Choroid Plexus neoplasms
Gliosarcoma
Pinealoma
Nervous System Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Nervous System Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009