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

Defining a Personalized Hypoxic Radiation Target Through Correlation of Functional F18-FAZA PET Imaging to Pimonidazole-stained 3D Whole-mounted Histological Specimen

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.

Study Overview

• Status: Suspended
• Conditions: Tongue Cancer
• Intervention / Treatment: Radiation: (18)F-Fluoroazomycin arabinoside; Drug: Pimonidazole

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre, Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: FAZA; Drug: Pimonidazole; oral pimonidazole hypoxia labeling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cellular hypoxia correlation	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	1 year
Hypoxic reference standard	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Registration quality	The quality of registration will be assessed through measuring registration error of various automatic and semi-automatic co-registration techniques	1 year
Textural feature comparison	Potential relationships between textural features of MRI, PET-CT, and immunohistochemistry will be evaluated.	1 year

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: University of Toronto; Sunnybrook Research Institute
• Investigators: Principal Investigator: Ian Poon, MD, FRCPC, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2018
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Oral Tongue Cancer; Tumor Hypoxia
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Mouth Neoplasms; Tongue Diseases; Tongue Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluoroazomycin arabinoside
• Other Study ID Numbers: FAITH 253-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No