Study of Intratumoral Hypoxia Using Pre-operative Administration of Pimonidazole
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|ClinicalTrials.gov Identifier: NCT01248637|
Recruitment Status : Completed
First Posted : November 25, 2010
Last Update Posted : July 30, 2018
|Condition or disease||Intervention/treatment|
|Pancreatic Cancer||Drug: Pimonidazole hydrochloride|
Intratumoral hypoxia (low oxygen concentration or pO2) occurs when oxygen consumption exceeds its delivery by the vascular system. Hypoxia is associated with adverse patient outcome in many human cancers and this association is hypothesized to be due to a combination of treatment resistance and aggressive tumor biology.
The study of hypoxia is also important as new cancer drugs are being developed that are specifically active on cancer cells in area of tumors with lower oxygen levels.
his study involves administering the hypoxia probe pimonidazole hydrochloride to patients prior to resection of pancreatic adenocarcinoma to evaluate the extent, molecular context and clinical relevance of hypoxia in clinical pancreatic cancer samples and the subsequently derived primary xenograft tumors.
We propose accrual of patients over a 5-year period to evaluate hypoxia within 100 clinical tumor specimens and corresponding primary xenograft tumours where available. The complementary techniques of wide-field multicolor fluorescence image analysis microscopy and high level flow cytometry will be used to identify potential relationships between intratumoral hypoxia and cell proliferation, differentiation, and the expression of putative cancer stem cell markers.
|Study Type :||Observational|
|Estimated Enrollment :||200 participants|
|Official Title:||A Clinical Trial of Intratumoral Hypoxia and Its Biologic Correlates in Patients Undergoing Surgical Resection of Localized Pancreatic Cancer, Using Pre-operative Administration of the Hypoxia Marker Pimonidazole.|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||December 2017|
|Actual Study Completion Date :||December 2017|
Oral pimonidazole is administered at a dose of 0.5gm/m2 once approximately 24 hrs prior to surgery
Drug: Pimonidazole hydrochloride
Pimonidazole is a 2-nitroimidazole that is selectively reduced and covalently binds to intracellular macromolecules in areas of hypoxia (by definition, p02 <= 10mm Hg) within normal and tumour tissue. Pimonidazole adducts can then be detected by immunolabelling techniques (microscopy, ELISA, flow cytometry etc). In this study, pimonidazole will be administered orally as a one time dose of 0.5gm/m2 24hrs prior to surgery. Since the drug has a half-life of approximately 5 hrs, this time-frame ensures low circulating levels at the time of surgery and therefore reduces the confounding effects of surgical hypoxia on tumour analysis.
Other Name: Hypoxyprobe-1
- characterization of intratumoral hypoxia in pancreatic cancer [ Time Frame: 5 Years ]estimation of tumoral hypoxic fraction by immunodetection of pimonidazole adducts.
- correlation of intratumoral hypoxia with patient survival rate [ Time Frame: 5 Years ]evaluation of correlation of tumoral hypoxia with disease-free survival using Cox proportional hazards analysis
- correlation of hypoxia with molecular markers [ Time Frame: 5 Years ]colocalization of molecular markers using immunofluorescence microscopy: Stem-cell like populations markers of EMT Endogenous markers of hypoxia (HIF1a, CAIX)
- to assess utility of circulating osteopontin and miR-210 for identifying hypoxia [ Time Frame: 5 Years ]correlation of tumoral hypoxic fraction with plasma levels of osteopontin and miR-210
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01248637
|Princess Margaret Cancer Centre|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Neesha Dhani, MD||Univeristy Health Network - Princess Margaret Cancer Centre|