Study of Intratumoral Hypoxia Using Pre-operative Administration of Pimonidazole

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by University Health Network, Toronto
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01248637
First received: November 24, 2010
Last updated: July 10, 2015
Last verified: July 2015
  Purpose

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 Intervention
Pancreatic Cancer
Drug: Pimonidazole hydrochloride

Study Type: Observational
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.

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • characterization of intratumoral hypoxia in pancreatic cancer [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    estimation of tumoral hypoxic fraction by immunodetection of pimonidazole adducts.

  • correlation of intratumoral hypoxia with patient survival rate [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    evaluation of correlation of tumoral hypoxia with disease-free survival using Cox proportional hazards analysis


Secondary Outcome Measures:
  • correlation of hypoxia with molecular markers [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    correlation of tumoral hypoxic fraction with plasma levels of osteopontin and miR-210


Biospecimen Retention:   Samples With DNA

Pancreatic Tumor biopsy and blood samples.


Estimated Enrollment: 100
Study Start Date: October 2010
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Participating in ICGC Pancreatic Cancer Genome Project.

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01248637

Contacts
Contact: Neesha Dhani, MD 416-946-4501 ext 2260 neesha.dhani@uhn.on.ca
Contact: David Hedley, MD 416-946-4501 ext 3428 david.hedley@uhn.on.ca

Locations
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Neesha Dhani, MD    416-946-4501 ext 2260    neesha.dhani@uhn.on.ca   
Principal Investigator: Neesha Dhani, MD         
Sub-Investigator: David Hedley, MD         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Neesha Dhani, MD Univeristy Health Network - Princess Margaret Cancer Centre
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01248637     History of Changes
Other Study ID Numbers: PIMO-PANC, UHN REB 10-0350-C
Study First Received: November 24, 2010
Last Updated: July 10, 2015
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by University Health Network, Toronto:
pancreas
pancreatic cancer
pancreatic tumor
pimonidazole
hypoxia
whipple's resection

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Pimonidazole
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015