Clinical trial NCT03181035: Correlation of FAZA PET Hypoxia Imaging To 3D Histology in Oral Tongue Cancer
Official title: Defining a Personalized Hypoxic Radiation Target Through Correlation of Functional F18-FAZA PET Imaging to Pimonidazole-stained 3D Whole-mounted Histological Specimen
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Tongue Cancer
Keywords: Oral Tongue Cancer
Tumor Hypoxia
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Sunnybrook Research Institute
name: University of Toronto
First posted: 2017-06-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cellular hypoxia correlation
timeFrame: 1 year
measure: Hypoxic reference standard
timeFrame: 1 year
Secondary outcomes:
measure: Registration quality
timeFrame: 1 year
measure: Textural feature comparison
timeFrame: 1 year
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Odette Cancer Centre, Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Ian Poon, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: