FAZA PET as Biomarker for Hypoxia in Rectal Cancer

NCT02624115 | Completed

• 1 other identifier: 15-9741
• Study Type: observational
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer (CRC) is one of the leading causes of cancer mortality in Canada. Rectal cancers are now known to be hypoxic which is a negative prognostic factor and predictive of metastatic spread and poor responsiveness to treatment. This has also been shown in preclinical xenograft models. Hence there is a need for identification of hypoxic rectal cancers. In this pilot study the investigators intend to non-invasively assess the tumor and nodal metastasis using an integrated Positron Emission Tomography-Magnetic Resonance Imaging scanner (PET/MRI) with 18F-Fluoroazomycin Arabinoside (18F-FAZA) a radiopharmaceutical for assessing tumor hypoxia. The hypoxic rectal tumors will show an increased uptake of 18F-FAZA on PET which will have morphological correlation on MRI. The patient will then undergo neoadjuvant chemoradiation therapy (CRT) followed by repeat 18F-FAZA PET/MRI and rectal cancer surgery with pimonidazole staining. Pimonidazole is an extrinsic marker of hypoxia that is selectively reduced and covalently bound to intracellular macromolecules in areas of hypoxia within normal and tumor tissue with current approval for use in humans for research studies. The primary goal of this pilot trial is to validate FAZA-PET as a biomarker of hypoxia by correlating its uptake in rectal tumors to pimonidazole staining in histopathology specimens. If the investigators pilot study successfully demonstrates the uptake and correlation of pimonidazole and FAZA-PET, the investigators would like to initiate a larger study examining hypoxia in rectal cancer. The investigators aims would be to image patients with locally advanced rectal cancer before CRT to ascertain whether high FAZA-PET uptake correlates with poor outcome to CRT. The ability to preoperatively predict the patient sub-population that will respond best to CRT, will help to identify the "complete pathological" responders and avoid unnecessary surgery. Furthermore, the FAZA-PET high subset of patients may benefit from other treatment strategies including clinical trials of anti-hypoxic agents.

Conditions

Colon Rectal Cancer Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• FAZA PET uptake in locally advanced rectal cancers prior to and after chemoradiotherapy

  FAZA uptake will be measured by Semiquantitative Uptake Value measurements as well as against a standard of reference (blood pool activity, physiological muscle uptake).

  1.5 years

Secondary Outcomes (1)

• Correlation of FAZA-PET and blood oxygen level-dependent MRI to Pimonidazole staining in locally advanced rectal cancer

  1.5 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with rectal cancer undergoing neoadjuvant chemoradiotherapy

You may qualify if:

• Age ≥18 years
• Histologic proven locally advanced rectal cancer (T3-T4, or N1) based on clinical assessment and standard staging procedures.
• Intention to treat with neoadjuvant chemoradiotherapy prior to surgery, according to the current institutional treatment policies.
• A negative urine or serum pregnancy test within the two week interval immediately prior to imaging, in women of child-bearing age.
• Ability to provide written informed consent to participate in the study (for both components of the trial: imaging with FAZA-PET/MR and administration of Pimonidazole).

You may not qualify if:

• Patients will be ineligible to participate in this study if they meet any of the following criteria:
• Contraindication for MR as per current institutional guidelines.
• Inability to lie supine for at least 45 minutes.
• Contraindication for administration of pimonidazole (allergy)
• Any patient who is pregnant or breastfeeding.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Study Officials

• Catherine O'Brien, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Ur Metser, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Month
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2015
• First Posted: December 8, 2015
• Study Start: May 1, 2016
• Primary Completion: June 9, 2019
• Study Completion: June 9, 2019
• Last Updated: August 16, 2019

Record last verified: 2019-08

Locations

CA (1)