Clinical trial NCT02367482: Tryptophan Metabolism in Human Brain Tumors-Novocure
Official title: Tryptophan Metabolism in Human Brain Tumors: For Patients Whose Clinical Treatment Includes NovoTTF
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Glioblastoma
Keywords: rGBM
Recurrent GBM
Recurrent Glioblastoma
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: NovoCure Ltd.
First posted: 2015-02-20
Enrollment: 20
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients eligible and agreeable to undergo NovoTTF treatment at KCC/WSU due to recurrent glioblastoma (initial or subsequent tumor recurrence) will be recruited by the multidisciplinary neuro-oncology team to undergo the two AMT-PET studies.

Brief summary: In this research study, we will track the build-up of tryptophan, a radioactive tracer, in the brain using positron emission tomography (PET) scanning. Tryptophan, in its natural state, is an amino acid (one of the building blocks of proteins) that is normally present in the brain, and is used by the brain cells to create various other compounds. This process is altered in the presence of a brain tumor. By using a form of tryptophan marked with a small amount of radiation, we will be able to track this process during the course of the PET scan. This research will help determine if AMT PET is a useful method to recognize and differentiate between various types of brain tumors. In addition, to study the mechanisms of altered tryptophan uptake in the tumor and brain, we will also measure tryptophan levels and related molecules in your blood (obtained as a part of the PET procedure) and tumor tissue (in case you will have surgery to remove the tumor). This will help us to find new approaches to treat brain tumors in the future by altering abnormal tryptophan metabolism.

Detailed description: If you agree to take part in this research study, you will be asked to have:

1. A PET scan, 2. brief clinical questionnaires, and 3. biochemical studies of blood and tumor tissue. You will also have a second PET scan later, 2-3 months after the start of NovoTTF therapy, to determine if there are changes in the tumor that can be detected by PET. Your ability to participate in the study will be based, in part, on the results of the magnetic resonance images (MRI) in your medical chart from earlier clinical procedures. Once we receive the results of the PET scan, these will be compared to the MRI in order to help us analyze the tryptophan uptake in your brain. It will take about 3 hours to complete the PET scan; this includes the completion of the questionnaire, preparation and scanning. The actual scanning time will be 70 minutes. If you are a female of child-bearing age, we will need a small urine sample from you before starting the PET scanning procedure to make absolutely sure that you do not have unknown pregnancy for which radiation exposure might be harmful.

1. The PET scan will be used to measure the accumulation of the injected radioactive tracer AMT in your brain. To make this measurement more accurate, we will use your clinically obtained MRI scan(s), which was used to diagnose the tumor, to identify the exact location and extent of the tumor. For the PET scan, an intravenous catheter (a small tube placed in your vein) will be inserted for the injection of the AMT for this PET scan. It is the tracer that the PET scanner "sees" when performing the scan. The amount of the tracer, which will be given is very small (5 ml, the volume of a teaspoon), and therefore no side effects are expected from the tracer itself. A second intravenous catheter will be inserted to collect blood samples during the scan; a total of less than 2 teaspoons of blood will be collected. Participants may be sedated (put into sleep with some medicine) if they are unable to remain still for the scanning period.
2. On the day of the PET scan, we will ask you to fill out a brief clinical questionnaire, and also an additional multiple-choice questionnaire to screen for potential mood problems (which often coincide with brain tumors). Participants with a potential speech (comprehension) problem will also be administered a brief speech test. The goal of these tests is to identify various clinical problems that can be associated with brain tumors and affected by abnormal tryptophan metabolism that we measure with the PET scan.
3. If you have surgery to remove the tumor, a portion of the removed tissue will be used for biochemical studies. The doctor will not remove more tissue than needed for your care. The blood (obtained during the PET scanning) and tumor tissue (obtained during surgery) will be processed for analysis and stored in a locked container or freezer in a laboratory. In addition, we will review the clinical pathology report, so that we can correlate your PET results to type and grade of the tumor.

Eligibility criteria: Inclusion Criteria:

1. Clinical and MRI diagnosis of recurrent GBM.
2. Age ≥22 years.
3. Patient agrees to NovoTTF treatment but has not started treatment yet.
4. Patient agrees to undergo a baseline and a follow-up AMT-PET scan during NovoTTF treatment.
5. Patient able to provide informed consent.

Exclusion Criteria:

1. Resective surgery within 2 months prior to the initial AMT-PET scan (acute/subacute post-surgical inflammatory changes may cause false positive increased uptake on AMT-PET).
2. Severe increased intracranial pressure, status epilepticus, or other severe complications of the tumor, requiring emergency or urgent intervention.
3. Positive pregnancy test (because of radiation involved in PET scanning).

Primary outcomes:
measure: Interval Changes of Tumoral Metabolism
timeFrame: 2-3 months
Secondary outcomes:
measure: Interval changes of tumoral tryptophan metabolism
timeFrame: 2-3 months
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
Study officials:
affiliation: Wayne State University
name: Csaba Juhasz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Sandeep Mittal, MD
role: PRINCIPAL_INVESTIGATOR
References: