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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

Tracking Information
First Submitted Date November 24, 2010
First Posted Date November 25, 2010
Last Update Posted Date July 30, 2018
Study Start Date October 2010
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 24, 2010)
  • 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
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT01248637 on Archive Site
Current Secondary Outcome Measures
 (submitted: November 24, 2010)
  • 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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title Study of Intratumoral Hypoxia Using Pre-operative Administration of Pimonidazole
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.
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.
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
Study Design Observational Model: Other
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Pancreatic Tumor biopsy and blood samples.
Sampling Method Non-Probability Sample
Study Population Participating in ICGC Pancreatic Cancer Genome Project.
Condition Pancreatic Cancer
Intervention 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
Study Groups/Cohorts Pimonidazole hydrochloride
Oral pimonidazole is administered at a dose of 0.5gm/m2 once approximately 24 hrs prior to surgery
Intervention: Drug: Pimonidazole hydrochloride
Publications * Dhani NC, Serra S, Pintilie M, Schwock J, Xu J, Gallinger S, Hill RP, Hedley DW. Analysis of the intra- and intertumoral heterogeneity of hypoxia in pancreatic cancer patients receiving the nitroimidazole tracer pimonidazole. Br J Cancer. 2015 Sep 15;113(6):864-71. doi: 10.1038/bjc.2015.284. Epub 2015 Sep 1.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Completed
Estimated Enrollment
 (submitted: March 31, 2017)
Original Estimated Enrollment
 (submitted: November 24, 2010)
Actual Study Completion Date December 2017
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

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)
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Canada
Removed Location Countries  
Administrative Information
NCT Number NCT01248637
Other Study ID Numbers PIMO-PANC
UHN REB 10-0350-C
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party University Health Network, Toronto
Study Sponsor University Health Network, Toronto
Collaborators Not Provided
Principal Investigator: Neesha Dhani, MD Univeristy Health Network - Princess Margaret Cancer Centre
PRS Account University Health Network, Toronto
Verification Date July 2018