A Feasibility, Dose-Escalation Study Using Intracerebral Microdialysis to Assess the Neuropharmacodynamics of Temsirolimus in Patients With Primary or Metastatic Brain Tumors

NCT00784914 | Completed Phase 1 DMC

• 4 other identifiers: 07064P30CA033572CHNMC-07064CDR0000617019
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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: The purpose of this study is to evaluate the feasibility of using a microdialysis catheter to see what effect temsirolimus has on various biological substances associated with brain tumors over time.

Conditions

Brain and Central Nervous System Tumors; Metastatic Cancer

Keywords

adult anaplastic astrocytoma; adult diffuse astrocytoma; adult craniopharyngioma; adult choroid plexus tumor; adult brain stem glioma; 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; meningeal melanocytoma; adult meningeal hemangiopericytoma; adult grade I meningioma; adult grade II meningioma; adult grade III meningioma; adult anaplastic oligodendroglioma; adult oligodendroglioma; adult pineoblastoma; adult pineocytoma

Outcome Measures

Primary Outcomes (2)

• Feasibility of using a microdialysis catheter to assess the neuropharmacodynamics (nPD) of temsirolimus

  Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately

• Changes in intracerebral levels of vascular endothelial growth factor (VEGF), interleukin-1ß (IL-1ß), and other cytokines

  Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately

Secondary Outcomes (4)

• Relationship between temsirolimus dose and changes in intracerebral levels of VEGF, IL-1ß, and other cytokines

  Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately

• Relationship between the degree of microvascular proliferation and the tensin homologue deleted on chromosome 10 (PTEN) status in tumor tissue

  30 days after placement of the microdialysis catheter.

• Relationship between changes in intracerebral cytokine levels after treatment with temsirolimus

  Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately

• Compare changes in intracerebral cytokine levels to changes in systemic cytokine levels.

  Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately

Study Arms (2)

Cohort 1

ACTIVE COMPARATOR

Patients do not receive temsirolimus.

Other: cytokine levels

Cohort 2

EXPERIMENTAL

48 hours after surgery, patients receive one 200 mg dose of temsirolimus IV.

Drug: temsirolimus; Other: pharmacological study; Other: cytokine levels

Interventions

temsirolimus DRUG

Receive temsirolimus IV

Cohort 2

pharmacological study OTHER

Plasma levels of temsirolimus and sirolimus will be evaluated in serial blood samples.

Cohort 2

cytokine levels OTHER

Dialysate samples are collected at regular intervals during the 96 hours following placement of the catheter to measure changes in levels of cytokines, chemokines and growth factors

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be at least 18 years of age.
• Patients must have either a primary or metastatic brain tumor(s).
• Patients must be in need of a surgical debulking or a stereotactic biopsy for the purpose of diagnosis or differentiating between tumor progression and treatment-induced effects following radiation therapy + or - chemotherapy.
• For patients in cohort 2, treatment with temsirolimus must not be contraindicated.
• Patients in cohort 2 must not be taking any hepatic enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine).
• Patients who are taking strong CYP3A4 inducers or inhibitors such as clarithromycin, itraconazole, ketoconazole, nefazodone, telithromycin, rifampin, rifabutin, rifampacin, or St. John's Wort must discontinue the medication beginning at least one week prior to surgery and lasting for the duration of the study. The only exception will be dexamethasone which can be used post-operatively as indicated.
• Patients must have a Karnofsky Performance Status \>= 60% or an ECOG/Zubrod score of\<= 2.
• Patients must have recovered from any toxicity of any prior therapy.
• Patients must have adequate bone marrow function (defined as an absolute neutrophil count of \>= 1500 cells/mm3 and platelet count ≥ 100,000 cells/mm3), liver function with total bilirubin \<= 2.0 mg/dl and AST (SGOT) \<= 4 times the institutional upper limit of normal, and serum creatinine \<=1.5 x the institutional upper limit of normal.
• Patients must be able to understand and be willing to sign a written informed consent document.
• The effects of temsirolimus on a developing fetus are unknown. Therefore, female patients of childbearing potential and sexually-active male patients must agree to use an effective method of contraception while participating in this study. Women of childbearing potential must have a negative pregnancy test \<=2 weeks prior to registration.

You may not qualify if:

• Patients must not be planning to receive radiation, other chemotherapy or participate in another clinical trial from the time of surgery until the microdialysis catheters is removed.
• Patients allergic to temsirolimus, sirolimus (rapamycin), or Dextran.
• Patients with a coagulopathy, increased susceptibility to infection or bleeding disorders.
• Patients on anticoagulant drug therapy.
• Patients with uncontrolled diabetes.
• Patients who have a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Female patients who are pregnant or breast-feeding.
• HIV-positive patients receiving anti-retroviral therapy are excluded from the study due to the possibility of PK interactions with temsirolimus; however, patients will not be routinely screened for HIV.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Neoplasm Metastasis; Astrocytoma; Craniopharyngioma; Choroid Plexus Neoplasms; Brain Neoplasms; Gliosarcoma; Glioblastoma; Neuroectodermal Tumors, Primitive; Medulloblastoma; Ependymoma; Glioma, Subependymal; Glioma; Meningioma; Oligodendroglioma; Pinealoma

Interventions

temsirolimus

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Cerebral Ventricle Neoplasms; Brain Diseases; Central Nervous System Diseases; Neoplasms, Vascular Tissue; Meningeal Neoplasms

Study Officials

• Jana Portnow, MD

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2008
• First Posted: November 4, 2008
• Study Start: June 1, 2008
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: April 17, 2018

Record last verified: 2018-04

Locations

US (1)