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Study of Intratumoral Hypoxia Using Pre-operative Administration of Pimonidazole

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01248637
Recruitment Status : Completed
First Posted : November 25, 2010
Last Update Posted : July 30, 2018
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:
This study involves the administration of a hypoxia marker, pimonidazole hydrochloride, taken orally approximately 24 hours before surgical resection of a pancreatic tumor in order to identify areas of lower oxygen content on tumor samples.

Condition or disease Intervention/treatment
Pancreatic Cancer Drug: Pimonidazole hydrochloride

Detailed Description:

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.

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Other
Time Perspective: Other
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

Resource links provided by the National Library of Medicine

Group/Cohort Intervention/treatment
Pimonidazole hydrochloride
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

Primary Outcome Measures :
  1. characterization of intratumoral hypoxia in pancreatic cancer [ Time Frame: 5 Years ]
    estimation of tumoral hypoxic fraction by immunodetection of pimonidazole adducts.

  2. 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

Secondary Outcome Measures :
  1. 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)

  2. 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
Pancreatic Tumor biopsy and blood samples.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participating in ICGC Pancreatic Cancer Genome Project.

Inclusion Criteria:

  • age > 18
  • provisional diagnosis of pancreatic cancer
  • scheduled resection at UHN
  • consented to ICGC Pancreatic Cancer Genome Project
  • surgery planned for >2 days away (drug administration has to be 16-20hrs before surgery)

Exclusion Criteria:

  • not participating in ICGC
  • contraindications to pimonidazole (allergy)
  • surgery scheduled for same or next day (not enough time to arrange for drug administration)

Information from the National Library of Medicine

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 identifier (NCT number): NCT01248637

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Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
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Principal Investigator: Neesha Dhani, MD Univeristy Health Network - Princess Margaret Cancer Centre
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University Health Network, Toronto Identifier: NCT01248637    
Other Study ID Numbers: PIMO-PANC
UHN REB 10-0350-C
First Posted: November 25, 2010    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: July 2018
Keywords provided by University Health Network, Toronto:
pancreatic cancer
pancreatic tumor
whipple's resection
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Signs and Symptoms, Respiratory