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Brain and Central Nervous System TumorsPhase 1NCT00784914

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

A Phase 1 study testing temsirolimus, pharmacological study and cytokine levels in people with Brain and Central Nervous System Tumors and Metastatic Cancer, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
temsirolimus, pharmacological study and cytokine levels
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
Jun 2008to Nov 2010
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010-3000

Other trials in United States

About this study

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

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.

Read the 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.
  • Compare changes in intracerebral cytokine levels to changes in systemic cytokine levels.
  • 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: Two cohorts of 6 patients will be enrolled in this study. 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 2 treatment cohorts.

  • Cohort 1: Patients do not receive temsirolimus. Dialysate samples will be collected at regular intervals during the 96 hours following placement of the catheter as well as serial blood samples to measure levels of cytokines, chemokines and growth factors that occur after neurosurgery.
  • Cohort 2: Beginning 48 hours after surgery, patients receive a single 200 mg dose of temsirolimus IV. Dialysate samples will be collected at regular intervals during the 96 hours following placement of the catheter as well as serial blood samples to measure levels of cytokines, chemokines and growth factors that occur after neurosurgery. Plasma levels of temsirolimus and sirolimus will also be measured from the serial blood samples.

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

Being tested
temsirolimus, pharmacological study, cytokine levels
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
Medical subject headings
Central Nervous System Neoplasms, Neoplasm Metastasis, Astrocytoma, Craniopharyngioma, Choroid Plexus Neoplasms, Brain Neoplasms, Gliosarcoma, Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • temsirolimusDrug

    Receive temsirolimus IV

  • pharmacological studyOther

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

  • cytokine levelsOther

    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

Study groups in NCT00784914
Study groupRoleWhat they receive
Cohort 1Active comparatorPatients do not receive temsirolimus.
Receives: Other: cytokine levels
Cohort 2Experimental48 hours after surgery, patients receive one 200 mg dose of temsirolimus IV.
Receives: Drug: temsirolimus; Other: pharmacological study; Other: cytokine levels

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

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

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

Secondary outcomes (4)

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

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

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

    Measured: 30 days after placement of the microdialysis catheter.

  3. Relationship between changes in intracerebral cytokine levels after treatment with temsirolimus

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

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2008 (estimated)
  2. Study startJun 2008
  3. Primary completionNov 2010
  4. Study completionNov 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00784914
Sponsor's protocol ID
07064
Other IDs
P30CA033572, CHNMC-07064, CDR0000617019
Status last verified
Apr 2018
First submitted
1 Nov 2008
Last updated
17 Apr 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing temsirolimus, pharmacological study and cytokine levels in people with Brain and Central Nervous System Tumors and Metastatic Cancer, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility of using a microdialysis catheter to assess the neuropharmacodynamics (nPD) of temsirolimus (time frame: Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00784914.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2018.

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