Colon Rectal Cancer Adenocarcinoma Clinical Trial
Official title:
18F-Fluoroazomycin Arabinoside (FAZA) Positron Emission Tomography/Magnetic Imaging Resonance (PET/MRI) as a Biomarker of Hypoxia in Rectal Cancer: A Pilot Study
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.
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 PET/MRI with a radiopharmaceutical for assessing tumor
hypoxia. The hypoxic rectal tumors will show 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 this 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 aim 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 subpopulation 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.
Project Synopsis: STUDY OVERVIEW:
OBJECTIVES:
Primary Objective
1. To determine the feasibility of using the FAZA-PET to image primary tumor hypoxia in
patients with rectal cancer prior to treatment with chemoradiotherapy Secondary
Objectives
2. To optimize FAZA PET/MRI imaging protocol for use in patients with rectal cancer.
3. To determine whether there is correlation between FAZA-PET, blood oxygen level-dependent
MRI and Pimonidazole staining in primary rectal tumors before and after CRT.
4. To correlate hypoxia defined by FAZA PET uptake and blood oxygen level-dependent MRI in
rectal cancer with (pathologic) response to neoadjuvant chemoradiotherapy.
Study design: Single arm feasibility pilot study Study scheme: (see below)
Details on Tumor Microscopy and Pimonidazole Image analysis:
The initial assessment of pimonidazole-detected hypoxia in tumor sections from surgical
specimens will be immunohistochemical which allows for both qualitative and quantitative
assessment of pimonidazole staining in the context of histopathological morphology. To
account for heterogeneity of pimonidazole staining, analysis will be performed in multiple
surgical sections for each patient tumor (as previously published by the investigators own
group). All staining, handling and processing of tissue specimens will done by the pathology
department.
STUDY SCHEMA:
Target Population:
- Age ≥ 18 years
- Histological diagnosis of rectal cancer
- Intent to treat with neoadjuvant chemoradiotherapy and surgery
- Negative pregnancy test (for females in child bearing age)
1. Informed Consent
2. FAZA-PET/MRI
- Void bladder
- FAZA injection
- Dynamic PET acquisition with MRI Dixon sequences for attenuation correction (60 min;
optional )
- 60 minute uptake time (rest)
- Void bladder
- Static PET/MRI pelvis (approximately 45 min)
3. Standard treatment (neoadjuvant chemoradiotherapy
4. Oral Pimonidazole on day prior to surgery
5. Surgery
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
NCT00767234 -
Permission to Collect Blood Over Time for Research
|
N/A |