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qBOLD MRI of Glioblastoma Multiforme for Assessment of Tumor Hypoxia.

Study Purpose

Glioblastoma multiforme (GBM) is the most common primary malignant brain neoplasm in adults. Despite recent diagnostic and therapeutic advances, including aggressive surgical resection and chemoradiation, the prognosis of GBM has improved only slightly over the past two decades, with median survival of approximately 15 months. Tumor hypoxia is a feature of GBM that contributes to poor outcome through multiple mechanisms such as 1) overexpression of enzymes that play roles in temozolomide resistance, the main chemotherapeutic agent in GBM and 2) increase expression of cancer stem cells which are more resistant to radiation. Hypoxic tumour regions are associated with higher rates of progression and recurrence. In this study the investigators will use an advanced MRI technique called qBOLD to non-invasively measure oxygenation in GBM and obtain targeted biopsies. The investigators take advantage of physical characteristics of Ferumoxytol (Feraheme®) which is an iron supplement, and utilize two recent technical advances not previously used in human tumours to quantitatively measure oxygenation in GBM. Prior knowledge of hypoxia can assist in prognostication and individualization of treatment planning with special focus on hypoxic regions by targeted radiation dose or regimen modulation; consideration of more intensive chemotherapy regimens; more aggressive and targeted surgical resection and closer short-term clinical and imaging follow-ups.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Adult (>18 year old) patients with newly diagnosed GBM presenting to our centre for surgical management and post-operative chemoradiation. 2. Creatinine clearance > 60 ml/minute. 3. Able to tolerate an MR scan. 4. Capable of providing informed consent.

Exclusion Criteria:

1. Prior brain surgery or radiation. 2. History of liver disease requiring liver MRI (due to accumulation of ferumoxytol in Kupffer cells which can affect liver MRI for up to 3 months) 3. On more than two antihypertensive medications. 4. History of allergy or adverse reaction to iron supplements. 5. Prior treatment with ferumoxytol. 6. Large (>50%) hemorrhagic component in the solid enhancing part of the tumor. 7. Need for emergency craniotomy. 8. Pregnant patients. 9. Breast feeding. 10. Serum ferritin of >800 ng/mL

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02466828
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Early Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Sunnybrook Health Sciences Centre
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Pejman Jabehdar Maralani, MD FRCPC
Principal Investigator Affiliation	Sunnybrook Health Sciences Center
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Completed
Countries	Canada
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Glioblastoma, Hypoxia

Additional Details

We propose a study to demonstrate quantitative oxygen saturation estimation in GBM is feasible with qBOLD and it correlates with established histopathological markers of hypoxia and angiogenesis, and targeted intraoperative oxygen measurement. All patients will undergo surgery as part of their standard treatment. By coregistering the hypoxia map on presurgical MRI we will be able to do the following: 1. Obtain targeted biopsies of the hypoxic areas and none hypoxic areas and correlate them with gold standard marker of tissue hypoxia by immunohistochemistry for hypoxia induced factor-1α (HIF-1α). 2. Draw Volumes of interests (VOI) over areas >0.5-cm3 (amenable to accurate intra-operative O2 measurement) with the lowest and highest oxygen saturation (SO2) values. VOIs will be then imported into the neuronavigation system (Stryker) for targeted placement of clinically approved Licox® oxygen-sensing probe (Integra NeuroSciences).

Arms & Interventions

Arms

Experimental: Single patient group receiving Feraheme®

Newly diagnosed GBM patients with no prior treatment will receive Feraheme® as MRI contrast agent

Interventions

Drug: - Feraheme®

Drug will be diluted in 50 cc normal saline and infused over 15-60 minutes depending on patient condition.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Status

Address

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5

St. Michael's Hospital, Toronto, Ontario, Canada