Study of Intratumoral Hypoxia Using Pre-operative Administration of Pimonidazole

July 27, 2018 updated by: University Health Network, Toronto

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Participating in ICGC Pancreatic Cancer Genome Project.

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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 Names:
  • Hypoxyprobe-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
characterization of intratumoral hypoxia in pancreatic cancer
Time Frame: 5 Years
estimation of tumoral hypoxic fraction by immunodetection of pimonidazole adducts.
5 Years
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
5 Years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
5 Years
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
5 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Neesha Dhani, MD, Univeristy Health Network - Princess Margaret Cancer Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (ACTUAL)

December 1, 2017

Study Completion (ACTUAL)

December 1, 2017

Study Registration Dates

First Submitted

November 24, 2010

First Submitted That Met QC Criteria

November 24, 2010

First Posted (ESTIMATE)

November 25, 2010

Study Record Updates

Last Update Posted (ACTUAL)

July 30, 2018

Last Update Submitted That Met QC Criteria

July 27, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PIMO-PANC
  • UHN REB 10-0350-C

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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