Study of Intratumoral Hypoxia Using Pre-operative Administration of Pimonidazole

Pancreatic Cancer Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01248637
• Other study ID #: PIMO-PANC
• Secondary ID: UHN REB 10-0350-
• Status: Completed
• Start date: October 2010
• Est. completion date: December 2017

Study information

• Verified date: July 2018
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Hypoxia
• Pancreatic Cancer
• Pancreatic Neoplasms

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.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	characterization of intratumoral hypoxia in pancreatic cancer	estimation of tumoral hypoxic fraction by immunodetection of pimonidazole adducts.	5 Years
Primary	correlation of intratumoral hypoxia with patient survival rate	evaluation of correlation of tumoral hypoxia with disease-free survival using Cox proportional hazards analysis	5 Years
Secondary	correlation of hypoxia with molecular markers	colocalization of molecular markers using immunofluorescence microscopy: Stem-cell like populations markers of EMT Endogenous markers of hypoxia (HIF1a, CAIX)	5 Years
Secondary	to assess utility of circulating osteopontin and miR-210 for identifying hypoxia	correlation of tumoral hypoxic fraction with plasma levels of osteopontin and miR-210	5 Years