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Correlation of FAZA PET Hypoxia Imaging To 3D Histology in Oral Tongue Cancer (FAITH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03181035
Recruitment Status : Recruiting
First Posted : June 8, 2017
Last Update Posted : October 22, 2021
Sunnybrook Research Institute
University of Toronto
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

Brief Summary:
This is a pilot study in the form of a prospective Phase II, single centre, single arm hypoxia study of oral tongue cancer with FAZA-PET imaging and pimonidazole targeted IHC of surgical specimens.

Condition or disease Intervention/treatment Phase
Tongue Cancer Radiation: (18)F-Fluoroazomycin arabinoside Drug: Pimonidazole Phase 1 Phase 2

Detailed Description:
In head and neck cancer, areas of tumours with low oxygen supply (called tumour hypoxia) harbour cells that are resistant to radiation and are prone to metastasize. Modern radiotherapy techniques are precise enough to deliver radiation to these small areas and could be used to target these areas to receive higher doses of radiation than the rest of the tumour to overcome resistance. Hypoxia can be "seen" in the body using special imaging such as [F-18]-FAZA-PET ([F-18]-Fluoroazomycin arabinoside positron emission tomography) but it has not been tested as a method for creating radiation treatment targets. As part of regular pathology tumour tissue is sliced extremely thinly (<1/100th of a millimeter) and stained so that individual cells can be seen under a microscope. Immunohistochemistry (IHC) is a special type of "stain" that can specifically highlight hypoxic areas. This method is considered the most accurate way to inspect for the presence of hypoxia. There is not a specific staining target for hypoxia ordinarily, but when patients ingest a substance called pimonidazole hydrochloride (HCl) it builds up specifically in hypoxic areas and can be targeted for IHC staining. In this study participants with oral tongue cancer will have a [F-18]-FAZA-PET scan and take a single dose of oral pimonidazole-HCl before having surgery to remove their cancer. The whole tumour will be used to create microscope slides using very thin slices of the tumour. The slices will be stained using IHC to show where the pimonidazole has built up and digital scans of the slides will be made. The hypoxia seen on the FAZA-PET scan will be "matched" with hypoxia on the electronic slides to see if the FAZA truly shows where hypoxia is in tumours and if it could be used as a way to plan radiation treatments to deliver more radiation to just those areas.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Defining a Personalized Hypoxic Radiation Target Through Correlation of Functional F18-FAZA PET Imaging to Pimonidazole-stained 3D Whole-mounted Histological Specimen
Actual Study Start Date : January 25, 2018
Estimated Primary Completion Date : December 30, 2023
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: FAZA and pimonidazole
(18)F-Fluoroazomycin arabinoside (FAZA) will be administered via intravenous injection at a dose of 5.2 MBq/kg with a minimum dose of 200 Megabecquerel (MBq) (5.4 Millicurie (mCi)) and a maximum dose of 600 MBq (16.2 mCi) prior to positron emission tomography (PET) imaging. A single dose of oral pimonidazole capsules at a dose of 0.5 g/m2, will be taken by participants 16-20 hours prior to tumor resection surgery.
Radiation: (18)F-Fluoroazomycin arabinoside
FAZA PET diagnostic testing
Other Name: FAZA

Drug: Pimonidazole
oral pimonidazole hypoxia labeling

Primary Outcome Measures :
  1. Cellular hypoxia correlation [ Time Frame: 1 year ]
    The degree to which hypoxic signal measured by FAZA-PET imaging is correlated with true cellular hypoxia confirmed by immunohistochemical staining of pimonidazole using a 3D whole-mount approach

  2. Hypoxic reference standard [ Time Frame: 1 year ]
    A reference standard hypoxic radiation target will be defined through the correlation of functional F18-FAZA PET imaging to a pimonidazole-stained 3D whole mounted histological specimen.

Secondary Outcome Measures :
  1. Registration quality [ Time Frame: 1 year ]
    The quality of registration will be assessed through measuring registration error of various automatic and semi-automatic co-registration techniques

  2. Textural feature comparison [ Time Frame: 1 year ]
    Potential relationships between textural features of MRI, PET-CT, and immunohistochemistry will be evaluated.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Biopsy proven Stage II-III oral tongue squamous cell carcinoma
  • Naïve to treatment for resectable disease
  • Surgical resection as definitive treatment modality
  • Ability to participate and willingness to give written informed consent prior to performance of any study-related procedures and to comply with the study protocol
  • Adequate hematologic, renal and liver function as defined by the following laboratory values up to 30 days prior to commencement of dosing (administration of FAZA):

    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    • Platelet count ≥ 50 ×109/L
    • Hemoglobin ≥ 9 g/dL
    • Bilirubin ≤ 1.5 × upper limit of normal (ULN) (20.0 µmol)
    • Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × the ULN (37 U/L, 40 U/L, 120 U/L)
    • Serum creatinine ≤ 1.5 × the ULN (106 µmol/L) or creatinine clearance ≥ 50 mL/min on the basis of the Cockroft-Gault glomerular filtration rate estimation: [(140-age) × (weight in kg × (0.85 if female)]/[72 × (serum creatinine in mg/dL)]
    • Prothrombin time (PT), international normalized ratio (INR), partial thromboblastin time (PTT) ≤ 1.5 × the ULN (respectively 1.1, 14 sec, 35 sec)
  • Negative serum pregnancy test within 14 days prior to commencement of dosing in women of childbearing potential. Women of non-childbearing potential need not undergo pregnancy testing. Female participants of childbearing potential agree to use adequate methods of contraception from the time of enrollment until 28 days after surgery. Clinically acceptable methods of birth control for this study include intrauterine devices (IUD), birth control pills, hormonal implants, injectable contraceptives, and using barrier methods such as condoms, vaginal diaphragm with spermicide, or sponge.

Exclusion Criteria:

  • Patients who have received prior chemotherapy or radiation therapy for their oral tongue carcinoma
  • Stage I, Stage III T1/N1/M0, and Stage IV disease
  • Pregnant or breastfeeding at the time of consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03181035

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Contact: Ian Poon, MD, FRCPC 416-480-6100 ext 4951

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Canada, Ontario
Odette Cancer Centre, Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Ian Poon, MD, FRCPC    416-480-6100 ext 4951   
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Sunnybrook Research Institute
University of Toronto
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Principal Investigator: Ian Poon, MD, FRCPC Sunnybrook Health Sciences Centre
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Responsible Party: Sunnybrook Health Sciences Centre Identifier: NCT03181035    
Obsolete Identifiers: NCT02519959
Other Study ID Numbers: FAITH 253-2015
First Posted: June 8, 2017    Key Record Dates
Last Update Posted: October 22, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sunnybrook Health Sciences Centre:
Oral Tongue Cancer
Tumor Hypoxia
Additional relevant MeSH terms:
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Tongue Neoplasms
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Fluoroazomycin arabinoside
Molecular Mechanisms of Pharmacological Action