Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Hypoxia

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Signs and Symptoms, Respiratory

Neuroepithelioma

Calculation of the oxygen saturation map of gliomas cases

MRI Oxygen Saturation Map

David Hassanein BERRO, MD

The imaging of cerebral oxygenation is an extremely important tool in understanding the pathophysiology of the tumor and for adaptation of therapies according to hypoxia. Currently, imaging of cerebral oxygenation is mainly performed by the use of Positron Emission Tomography (PET). Thus, the investigators have been able to show that the FMISO radiotracer can reveal tumor hypoxia (HypOnco study, promotor: Caen University Hospital, main investigator: J.S. Guillamo). After injection of the radiotracer, increased uptake is observed in the regions for which the tissue oxygen pressure is less than 10 mmHg (the healthy brain with a tissue oxygen pressure (ptO2) ≈ 40mmHg).

Although PET is a reference methodology, it is not widely practiced mainly because of radioactive sources. Magnetic Resonance Imaging (MRI) would bypass the previously mentioned PET limitations. The investigators have recently shown that a measure of local oxygen saturation could be obtained by MRI.

This methodology has also been implemented at a clinical scale on lower field MRI magnets, but its formal validation in a clinical situation remains to be demonstrated with respect to FMISO.

The major advantage of this methodology is that MRI is already performed in routine practice for patients. Measuring tissue oxygenation with MRI (SatO2-MRI) would not add additional examination for the patient. In addition, MRI is a non-ionizing methodology with a very good spatial resolution compared to PET, this should help to better understand intratumoral heterogeneity. Similarly, in preclinical studies, the investigators have shown in a context of mild hypoxia that SatO2-MRI may be more sensitive than PET.

The investigators propose a study to compare in patients with glial tumors, images obtained by 3 Tesla MRI of SatO2-MRI to the hypoxia maps obtained by FMISO PET. These imaging studies will be confronted with studies carried out in immunohistochemistry on biopsies / resection allowing to reveal and to quantify by image analysis the expression of the factors induced by hypoxia (HIF1, HIF2).

This study should include 20 patients with glioma (15 high-grade patients and 5 low-grade patients) in pre-surgery. The aim is to show that SatO2-MRI is a relevant methodology (in terms of sensitivity, specificity) for assessing intratumoral oxygenation in a context of brain tumors. This fits perfectly into an era of personalized medicine where functional imaging finds its meaning.

Multimodal Imaging of Hypoxia in Gliomas

Validation of SatO2-MRI as a reliable imaging method to detect hypoxic regions, in comparison with FMISO PET. This will mainly be done by measuring spatial correlation of hypoxic regions obtained by the two imaging modalities.

To correlate imaging biomarkers with more conventional approaches on tissue slices (immunohistochemistry HIF1 / HIF2 / CD34)

University Hospital, Caen

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Standard of care treatment for patients undergoing definitive chemoradiation for oropharyngeal squamous cell carcinoma

De-escalated radiation therapy for patients undergoing surgery to the primary site followed by chemoradiation to the primary site and neck for oropharyngeal squamous cell carcinoma

Surgical resection of primary oropharyngeal tumour followed by de-escalated radiation therapy (30Gy) with concurrent platinum-based chemotherapy to oropharynx + neck, followed by surgical neck dissection

De-escalation

Radiation therapy (70Gy) with concurrent platinum-based chemotherapy to oropharynx + neck

Standard of care

Carol Kwong

Anna Lawless

Sarah Bergamin

The goal of this prospective clinical trial is to determine if HPV-associated oropharyngeal squamous cell carcinoma that is non-hypoxic on FMISO PET can be successfully treated with a lower dose of radiation therapy.

The main questions it aims to answer are:

1. What is the pathologic complete response rate in patients selected for radiation dose de-escalation and neck dissection?
2. What is the correlation between MRI and FMISO PET assessment of hypoxia before and during RT?
3. What are the acute and late toxicities in patients selected for radiation dose de-escalation?
4. What are the quality of life scores in patients selected for radiation dose de-escalation?
5. What are the local, regional and distant failure rates of patients selected for radiation dose de-escalation?

Patients with cT1-2N1-2b (AJCC 7th edition) oropharyngeal tumours will undergo surgical resection of the primary tumour. Following this, they will be allocated to standard radiation therapy (70Gy with concurrent cisplatin chemotherapy) or de-escalation radiation therapy (30Gy with concurrent cisplatin chemotherapy) based on the results of FMISO PET. Patients with non-hypoxic tumours at baseline OR after two weeks of radiation therapy will be allocated to the de-escalated group. 3-4 months after completion of radiation therapy, all patients in the de-escalated group will undergo mandatory neck dissection to assess pathologic response.

Researchers will assess the pathologic response rate after surgery in the de-escalation group. They will also compare the outcomes (oncological outcomes and quality of life) between the group receiving the standard treatment (70Gy) and the group receiving de-escalated radiation therapy (30Gy).

This study is designed to evaluate the role of FMISO PET in selecting patients for de-escalated RT. Patients with cT1-2N-1-2b HPV+ OPC or cTxN1-2 CUP, who are suitable for surgical management of the primary (if applicable) and/or RT to the primary and ipsilateral neck will be included. All patients will undergo surgical resection or core biopsy of the primary site if applicable (negative margins and robotic surgery not mandated) or EUA and tonsillectomy (CUP) and FNA or core biopsy of the cervical lymph node (all patients). Patients will be eligible for inclusion if histopathology is consistent with HPV-associated squamous cell carcinoma or CUP, with p16 positivity (IHC) and HPV positivity (PCR).

Patients enrolled will undergo FMISO PET/CT (after surgery to the primary or EUA/biopsy of suspected primary site) to assess for tumour hypoxia, which will stratify patients into two groups. Determination for the presence or absence of hypoxia will be made on the basis of visual inspection and in accordance with well-established tumour-muscle activity ratio (\>1.2) on the late static 18F-FMISO PET by 1 nuclear medicine physician. FMISO PET will be repeat after 5-10 fractions of RT (1-2 weeks of treatment) with the same assessment for hypoxia.

Absence of pre-treatment hypoxia or intra-treatment resolution of hypoxia on FMISO PET will be deemed as an indicator of radiosensitivity and qualify a patient for de-escalation (i.e., to total dose 30Gy). The remainder of patients (i.e., with evidence of tumour hypoxia at the FMISO PET performed after 5-10 fractions of RT) will continue to standard of care RT to a total dose of 70Gy.

Additional MRI images (including T1, T2 and dynamic contract-enhanced and oxygen enhanced sequences) before and during RT (at the same time as 18F FMISO PET). These will not change the patient's management.

All patients will undergo routine FDG-PET/CT scan three months after RT (as part of standard of care). Patients in the de-escalation arm will undergo mandatory ipsilateral neck dissection within 3-4 months of completing RT to assess for pathologic response. Patients will be followed up for a minimum of five years post treatment.

De-escalation of Radiation Dose in HPV-associated OPC Utilising FMISO PET (DE-RADIATE)

De-escalation of Radiation Dose in HPV-associated Oropharyngeal Squamous Cell Carcinoma Utilising FMISO PET and Magnetic Resonance Imaging as Non-Invasive Biomarkers of Hypoxia (DE-RADIATE)

Pathologic complete response in surgical neck dissection

Correlation between MRI and FMISO PET assessment of hypoxia at baseline and during radiation therapy

Quality of Life - Global (assessment by EORTC QLQ-30)

Quality of Life - Head \& Neck Specific (assessment by EORTC HN-35)

Failure rate at primary site (oropharynx) (calculated from date of commencing RT)

Failure rate in neck (calculated from date of commencing RT)

Number of participants with radiologically confirmed distant metastases (calculated from date of commencing RT)

Acute toxicities of radiation therapy +/- chemotherapy (assessed by CTCAE V 5.0)

Royal North Shore Hospital

Radiation Oncology Fellow & Principal Investigator

Recurrence

Glioblastoma

Disease Attributes

Astrocytoma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Lomustine

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

* Bevacizumab:

  -- Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
* FMISO PET Scan

  * FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
  * The PET scan will be approximately 60-75 minutes.
* MRI -- Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

Bevacizumab + CCNU:

* Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
* CCNU will be administered at a dose of 110 mg/m2 every 42 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).

  -FMISO PET Scan
* FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
* The PET scan will be approximately 60-75 minutes.

  - MRI
* Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

FMISO PET

MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

A cycle is defined as 28 days (1 month). The study duration is 12 months (12 cycles). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.

CCNU

Elizabeth Gerstner, MD

In this research study, the investigators are using FMISO-PET and MRI scans to explore the delivery of bevacizumab to the blood vessels in patient's with recurrent glioblastoma before and after treatment.

Bevacizumab is approved by the U.S. Food and Drug Administration for use in patients with recurrent glioblastoma . It works by targeting a specific protein called VEGF, which plays a role in promoting the growth or spreading of tumor blood vessels. Since anti-VEGF agents also affect normal blood vessels in the brain, they can inhibit the way other drugs used in combination with bevacizumab are delivered to the tumor.

In PET scans, a radioactive substance is injected into the body. The scanning machine finds the radioactive substance, which tends to go to cancer cells. For the PET scans in this research study, the investigators are using an investigational radioactive substance called FMISO. "Investigational" means that the role of FMISO-PET scans is still being studied and that research doctors are trying to find out more about it. FMISO goes to areas with low oxygenation so parts of the tumor that do not have enough oxygen can be seen.

In addition, a vascular MRI will be used to evaluate the changes in tumor blood flow, blood volume, and how receptive blood vessels are. This scan will be performed at the same time of the FMISO-PET scan.

This study does not add any additional treatment to patients with malignant glioma who are already scheduled to receive bevacizumab monotherapy. All treatment decisions will be at the discretion of the treating physician. There will be no change in the diagnosis or management of the patient based on any procedures or tests carried out as a part of this study.

If the participant chooses to take part in this research study each treatment cycle will last 28 days.

* Day 1-The participant will have the following procedures done before they can receive bevacizumab:

  * An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans
  * Blood pregnancy test for women of childbearing potential.
* Day 14:The participant will have the following procedures done after they receive bevacizumab:

  * An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans before the participant have received bevacizumab
  * Blood pregnancy test for women of childbearing potential.
* Day 28: The participant will have the following procedures done after they receive bevacizumab:

  * An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans after the participant has received bevacizumab
  * Blood pregnancy test for women of childbearing potential.

FMISO-PET Scans:

* The participant will have the scans performed in Charlestown, MA at the Martinos Center. The participant will be injected with two separate intravenous (IV) injections (listed below). Intravenous means a need will be injected into a vein in the participant's arm.

  * FMISO for PET scan and a contrast dye for the MRI scan
  * Drawing blood to assess the radioactivity of FMISO
* The PET scan will take approximately 60-75 minutes. The participant will receive one injection of FMISO. Following the injection of the radiotracer, blood samples will be taken from the second IV line. The tracer is given through a vein (IV) and travels through the participant's blood and collects in organs and tissues. The participant will need to wait nearby as the tracer is absorbed by the their body. This takes about 90 minutes. Then, the participant will lie on a narrow table that slides into a large tunnel-shaped scanner. The PET will pick up signals from the tracer and a computer will change the signals into 3D pictures that will be displayed on a monitor for the participant's study doctor to read.

MRI Scan:

* MRI scans will last about 60-75 minutes. This will occur at the same time as the PET scan. The participant will be injected with contrast dye twice during the MRI scan. The participant will have 3 MRI scans (prior to starting treatment, day 1 of treatment and day 14 of treatment) that would not have routinely been performed if the participant were not participating in this study.
* Blood samples will be collected during both scans in order to measure how the participant blood vessels are processing the radiotracer FMISO and how well it is being delivered to the tumor tissue.
* The participant will be assessed for side effects via clinic visit or phone call about 24 hours after each of the visits above.

Planned Follow-up: The investigators would like to call the participant every 3 months for three years after the 28 day visit to see how they are doing and if the participant is experiencing any side effects. If the participant is removed from the study due to an unacceptable side effect, the participant will be followed until it has been resolved.

FMISO PET Study of Glioblastoma

A Study to Evaluate Vascular Normalization in Patients With Recurrent Glioblastoma Treated With Bevacizumab Using FMISO PET and Vascular MRI

In this research study, the investigators are using FMISO-PET and MRI scans to explore the delivery of bevacizumab to the blood vessels in patient's with recurrent glioblastoma before and after treatment.

In this research study, the investigators are using FMISO-PET and MRI scans to explore the delivery of bevacizumab to the blood vessels in patient's with recurrent glioblastoma before and after treatment. Regional hypoxic volume (HV) was determined by thresholding the ratio of the standardized uptake values (SUV) of FMISO in the brain to cerebellum above 1.2. Since some patients had multiple tumors, we identified the HV region within the union of each contrast enhancing region of interest (ROI) and its surrounding FLAIR ROI, so individual tumors could be evaluated separately. HV represents the magnitude of hypoxia within each tumor.

The DCE-MRI data were processed using in-house custom software written in MATLAB to obtain maps of Ktrans based on the 2-parameter Tofts model. Population-level arterial input functions (AIFs) were used for DCE analysis; DCE was used only to calculate Ktrans. Median tumor values for Ktrans were calculated from the contrast enhancing region of interest (ROI). Higher value is more permeability.

This outcome measure looks at what blood flow was doing in tumor regions that were hypoxic. This outcome measured blood flow to the tumor using an MRI technique called dynamic susceptibility contrast enhancement that measures how fast injected contrast material flows through the tumor. This outcome specifically explored how blood flow to the tumor influenced tumor hypoxia.

National Cancer Institute (NCI)

Massachusetts General Hospital

Principal Investigator

Adverse event data was systematically assessed by regular investigator assessment and laboratory testing. Protocol only collected adverse events related to FMISO-PET scan, within 24 hrs (+/- 6 hrs) post-scan.

Bevacizumab:

* Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).

  -FMISO PET Scan
* FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
* The PET scan will be approximately 60-75 minutes.

  -MRI
* Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

FMISO PET

MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

Bevacizumab: A cycle is defined as 28 days (1 month). The study duration is 12 months (12 cycles). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.

FMISO PET & MRI Group 1

Bevacizumab + CCNU:

* Bevacizumab administered at dose of 10 mg/kg IV every 14 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.
* CCNU administered at dose of 110 mg/m2 every 42 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.

  -FMISO PET Scan
* FMISO intravenously injected at dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. IV will remain in place for injection of gadolinium for MRI scan. One injection of FMISO in PET protocol. Approximately 90 min after injection, PET scan will begin.
* PET scan will be approximately 60-75 minutes

  - MRI
* Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs.

FMISO PET

MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs.

FMISO PET & MRI Group 2

Bevacizumab:

* Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).

  -FMISO PET Scan
* FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
* The PET scan will be approximately 60-75 minutes.

  - MRI
* Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

FMISO PET

MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

Bevacizumab: A cycle is defined as 28 days (1 month). The study duration is 12 months (12 cycles). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Baseline

Day 14 (Week 2)

FMISO PET & MRI (Combined Groups)

Group 1 (Bevacizumab monotherapy) enrolled 2 patients. Group 2 (Bevacizumab+Lomustine) enrolled 9 patients. Any analysis per arm would be meaningless so the outcome data for both groups were lumped together. There was no pre-specified analysis plan to analyze the cohorts separately. Due to production challenges with FMISO, only 4 patients underwent all 3 FMISO-PET scans: baseline, day 14, and day 28. All 4 patients were in Group 2. The remaining 7 patients had MRI scans alone at those visits.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Multimodal Imaging of Hypoxia in Gliomas	NCT03716986	Glioma	MRI Oxygen Satu...	18 Years -	University Hospital, Caen
De-escalation of Radiation Dose in HPV-associated OPC Utilising FMISO PET (DE-RADIATE)	NCT06307015	HPV Positive Or...	De-escalation Standard of car...	18 Years -	Royal North Shore Hospital
De-escalation of Radiation Dose in HPV-associated OPC Utilising FMISO PET (DE-RADIATE)	NCT06307015	HPV Positive Or...	De-escalation Standard of car...	18 Years -	Royal North Shore Hospital
FMISO PET Study of Glioblastoma	NCT02076152	Recurrent Gliob...	FMISO PET MRI Bevacizumab CCNU	18 Years -	Massachusetts General Hospital
Multimodal Imaging of Hypoxia in Gliomas	NCT03716986	Glioma	MRI Oxygen Satu...	18 Years -	University Hospital, Caen

Spots Global Cancer Trial Database for fmiso pet

Every month we try and update this database with for fmiso pet cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for fmiso pet

Every month we try and update this database with for fmiso pet cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for fmiso pet cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.