Fluorescence Guided Resection of Brain Tumors

NCT ID: NCT00870779

Last Updated: 2019-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2013-07-02

Brief Summary

Removing a tumor from your brain is hard to do because, very often, brain tumors do not have boundaries that are easy for your surgeon to find. In many cases, the surgeon can't tell exactly where the tumor begins or ends. The surgeon usually can remove most of your tumor by looking at the MRI images that were taken of your brain before surgery. However, the surgeon does not have any good way to tell if the entire tumor has been removed or not. Removing the entire tumor is very important because leaving tumor behind may allow it to grow back which could decrease your chances of survival.

It is possible to detect tumor cells by making them glow with a specific color of light (a process called fluorescence). This can be done by having you take the drug, ALA, before your surgery. ALA is a molecule that already exists in the cells of your body. Once enough of it is in your body, it gets converted into another molecule named PpIX. If blue light is shined on a tumor that has enough PpIX, it will glow with red light (fluorescence) that can be detected with a special camera. In this study, we want to determine how the fluorescence (red light) is related to the tumor which appears in the images that are normally taken of your brain (which the surgeon uses to guide the removal of your tumor) and the tumor tissue that will be removed during your surgery. Removing the entire tumor is very important because leaving tumor behind may allow it to grow back which could decrease your chances of survival.

Detailed Description

The first phase of study (Stage I) will use FI coregistered with pMR, iUS and iSV images to test the overall hypothesis that there is a high degree of spatial correlation between local tissue FI signal and coregistered conventional imaging and corresponding histopathology. Additionally, coregistered probe measurements and biopsy specimens will be acquired intraoperatively. Biopsy specimens will be processed post-operatively (via fluorescence microscopy and chemical spectrofluorimetry) to assess PpIX concentration which will allow direct comparisons of FI signal strength with PpIX production (based on both in vivo probe data and ex vivo histological quantification) as a function of histological grade. The study protocol is outlined below. Because of the overall interest and importance of relating this data to the existing body of literature and the excellent safety record of oral administration of ALA reported in these trials [1, 33-36], we will use the same dose/time schedule described in [1, 33]. The operative procedures will follow existing practice at Dartmouth for image-guided resection of meningiomas, pituitary adenomas and metastases with additional acquisition of FI and biopsy data at predefined time points that are related to the expected volume of tumor tissue. In this first phase of the study, resection decisions will not be made based on FI data alone. Should residual fluorescence remain after the intended resection volume has been removed further excisions will require biopsy confirmation in the OR. It is anticipated that 234 patients will be enrolled in Stage I.

Conditions

Brain Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

5-aminolevulinic acid

Group Type: EXPERIMENTAL

5-aminolevulinic acid

Intervention Type: DRUG

20mg/kg 3 hours prior to surgery

Interventions

5-aminolevulinic acid

20mg/kg 3 hours prior to surgery

Intervention Type: DRUG

Other Intervention Names

5-ALA

Eligibility Criteria

Inclusion Criteria

• Preoperative diagnosis of either presumed low or high grade glioma (astrocytoma, oligodendroglioma, mixed oligo-astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme) or meningioma, pituitary adenoma or metastasis.
• Tumor judged to be suitable for open cranial resection based on preoperative imaging studies.
• Patient able to provide written informed consent.
• Age ≥ 21 years old.

Exclusion Criteria

• Pregnant women or women who are breast feeding
• History of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis
• History of liver disease within the last 12 months,
• AST, ALT, ALP or bilirubin levels greater than 2.5 times the normal limit at any time during the previous 2 months
• Plasma creatinine in excess of 180 mol/L.
• Inability to comply with the photosensitivity precautions associated with the study
• Patients with an existing DSM-IV Axis 1diagnosis
• Inability to give informed consent

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

David W. Roberts

OTHER

Sponsor Role: lead

Responsible Party

David W. Roberts

Professor of Surgery (Neurosurgery)

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David W Roberts, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Keith Paulsen, PhD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Countries

United States

Other Identifiers

R01NS052274-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DMS 0711

Identifier Type: -

Identifier Source: org_study_id