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

Tongue Cancer Clinical Trial

— FAITH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03181035
• Other study ID #: FAITH 253-2015
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 25, 2018
• Est. completion date: June 30, 2024

Study information

• Verified date: December 2022
• Source: Sunnybrook Health Sciences Centre
• Contact: Ian Poon, MD, FRCPC
• Phone: 416-480-6100
• Email: ian.poon[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT02519959

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: June 30, 2024
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Tongue Cancer
• Tongue Neoplasms

Intervention

Radiation:
• (18)F-Fluoroazomycin arabinoside
FAZA PET diagnostic testing

Drug:
• Pimonidazole
oral pimonidazole hypoxia labeling

Locations

Country	Name	City	State
Canada	Odette Cancer Centre, Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Sunnybrook Research Institute, University of Toronto

Country where clinical trial is conducted

Canada, 

Outcome

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