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(11C)dLop as a Marker of P-Glycoprotein Function in Patients With Gliomas

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01281982
First received: January 21, 2011
Last updated: February 19, 2014
Last verified: September 2012
  Purpose

Background:

- The blood-brain barrier helps to protect the central nervous system (brain and spinal cord) from harmful toxins, but also prevents potentially useful chemotherapy from reaching brain tumors. The barrier is formed by tight connections between blood vessel cells and molecules found on the surface of brain blood vessels such as Permeability-glycoprotein (Pgp). Pgp may influence whether patients with brain tumors known as gliomas respond to chemotherapy and what side effects they may experience. The compound (11C)N-desmethyl-loperamide ((11C)dLop) reacts to Pgp molecules, and therefore may be used with positron emission tomography (PET) imaging to study the blood brain barrier.

Objectives:

- To study the ability of PET imaging with (11C)dLop to evaluate the blood brain barrier in brain tumor patients.

Eligibility:

- Individuals at least 18 years of age who have a brain tumor with characteristics that may be imaged with techniques such as magnetic resonance imaging (MRI) andPET.

Design:

  • Participants will be screened with a full physical examination and medical history, blood and urine tests, and tumor imaging studies (fluorodeoxyglucose PET and MRI scans with contrast agent).
  • The (11C)dLop scan will take 1 hour to perform. Participants will be asked to return for blood and urine tests approximately 24 hours after the PET scan.
  • Participants will have followup visits at least every 4 months by repeating a complete history and physical exam and brain MRI. Participants may have repeat scans with (11C)dLop at various points in the course of cancer treatment, but will not have these scans more than twice in a 12-month period.
  • Participants will be followed for as long as possible during treatment to see if imaging with (11C)dLop correlates with response to the treatments....

Condition
Low Grade Glioma
Glioblastoma Multiforme
Anaplastic Astrocytoma
Anaplastic Oligodendroglioma
Oligoastrocytoma

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: (11C)N-Desmethyl-Loperamide as a Marker of P-Glycoprotein Function in Patients With Gliomas

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 2
Study Start Date: January 2011
Estimated Study Completion Date: September 2012
Detailed Description:

BACKGROUND:

A potential impedance to successful glioma chemotherapy is sanctuary for tumor behind the blood brain barrier. P-glycoprotein (Pgp) is an efflux transporter encoded by MDR1 that contributes to the functional regulation of substrates across the cerebrovasular endothelium. Pgp activity in patients with gliomas may influence response to therapy and neurotoxicity. (11C) N-desmethyl-loperamide (11C)dLop) is a radioligand substrate for Pgp, and PET imaging with this molecular marker may provide a non-invasive, in vivo method of examining Pgp function in brain tumor patients.

OBJECTIVES:

Primary:

-To measure the uptake of (11C)N-desmethyl-loperamide ((11C)dLop) using PET imaging as a marker of Pglycoprotein function in patients with intracranial gliomas

Secondary:

  • Correlate (11C)dLop PET uptake with perfusion MRI parameters and FDG PET uptake for volumes of interest (VOI) determined by the baseline MRI
  • Develop exploratory data for the correlation of (11C)dLop PET imaging with patient outcomes such as response to therapy, survival, and neurotoxicity
  • Develop exploratory data for the correlation of (11C)dLop PET imaging with immunohistochemical and molecular genomic assays of MDR1 and Pgp

ELIGIBILITY:

Patients with predominantly non-enhancing intracranial gliomas will be eligible.

DESIGN:

This is a pilot study of (11C)dLop PET imaging in 10 patients with intracranial glioma. Standard uptake values (SUVs) corrected for cerebral blood flow determined by (15O)H20 PET scans will be correlated to DCE-MRI (obtained within prior 2 weeks) and FDG-PET (obtained within prior 4 weeks) to characterize locoregional differences in Pgp function. When available, correlative studies performed on archived tumor tissue acquired immediately subsequent to (11C)dLop scanning will include immunohistochemical assays of Pgp expression, as well as characterization of MDR1 polymorphisms. Patient case histories will be followed longitudinally to make observations about how (11C)dLop imaging may correlate with patient outcomes such as response to therapy, survival, and neurotoxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Patients with histologically proven intracranial glioma will be eligible for this protocol. Eligible histologies include glioblastoma multiforme (GBM), gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), malignant astrocytoma NOS (not otherwise specified), low grade astrocytoma (LGA), low grade oligoastocytoma (LOA), and low grade oligodendroglioma (LGO). Patients with radiographically diagnosed or suspected low grade glioma will also be eligible.
  • Patients having undergone recent resection will be eligible as long as all of the following conditions apply:

    • They have recovered from the effects of surgery, not to have been performed within 2 weeks of the study scan.
    • Residual enhancing or non-enhancing disease following resection of recurrent tumor is mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done:
    • no later than 96 hours in the immediate post-operative period, or
    • at least 4 weeks post-operatively, and
    • within 14 days of registration, and
    • on a steroid dosage that has been stable for at least 5 days.
  • Normal organ and marrow function defined as: total leukocyte count greater than or equal to 3000 cells/ul, ANC greater than or equal to 1500 cells/ul, platelet count greater than or equal to 100,000 cells/ul, serum creatinine less than or equal to 2.0 X upper limit of normal, and bilirubin less than or equal to 1.5X upper limit of normal, hemoglobin greater than or equal to 9.0 g/dL , serum calcium less than12.0 mg/dL, AST/ALT less than or equal to1.5 times the upper limit of normal, PT less than or equal to1.5 ULN.
  • All patients or their previously designated DPA (if the patient is deemed by the treating physician to be impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) must sign an informed consent indicating that they are aware of the investigational nature of this study.
  • Patients must be greater than or equal to 18 years old.
  • Patients must have a Karnofsky performance status of greater than or equal to 60.
  • Patients must not have any significant medical illnesses that in the investigator s opinion cannot be adequately controlled with appropriate therapy or would compromise the patients ability to tolerate this study.
  • This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No exclusion to this study will be based on race. Minorities will actively be recruited to participate.

EXCLUSION CRITERIA:

  • Patients who, in the view of the treating physician, have significant active cardiac, hepatic, renal, or psychiatric diseases are ineligible.
  • Patients who have an active infection.
  • Pregnant (positive pregnancy test) or nursing women.
  • Patients cannot take loperamide within three days of (11C)dLop imaging.
  • Concurrent use of a Pgp inducer as listed in Appendix A within 2 weeks of a study scan. Use of these medications is allowed over the course of participation in the study, but must not be administered within 2 weeks of the study imaging.
  • Prior participation in other research protocols or clinical care in the last year such that radiation exposure, including that from this protocol, would exceed the guidelines set by the Radiation Safety Committee (RSC).
  • Patients who have any contraindication to gadolinium enhanced MRI.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01281982

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Teri N Kreisl, M.D. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01281982     History of Changes
Other Study ID Numbers: 110081, 11-C-0081
Study First Received: January 21, 2011
Last Updated: February 19, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Imaging
Gliomas
Pet Scan
Blood Brain Barrier
P-Glycoprotein
Brain Tumor
Glioma
Glioblastoma Multiforme
Astrocytoma

Additional relevant MeSH terms:
Astrocytoma
Glioblastoma
Glioma
Oligodendroglioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Krestin
Adjuvants, Immunologic
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Interferon Inducers
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Radiation-Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014