Study of Intratumoral Hypoxia Using Pre-operative Administration of Pimonidazole

Completed

• Conditions: Pancreatic Cancer
• Interventions: Drug: Pimonidazole hydrochloride

• Registration Number: NCT01248637
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2010-10
• Study First Submitted: 2010-11-24
• Study First Submitted QC: 2010-11-24
• Study First Posted: 2010-11-25
• Primary Completion: 2017-12
• Study Completion: 2017-12
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-27
• Last Update Posted: 2018-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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)

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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)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Pimonidazole hydrochloride	Pimonidazole hydrochloride	Oral pimonidazole is administered at a dose of 0.5gm/m2 once approximately 24 hrs prior to surgery

Primary Outcome Measures

Name	Time	Method
characterization of intratumoral hypoxia in pancreatic cancer	5 Years	estimation of tumoral hypoxic fraction by immunodetection of pimonidazole adducts.
correlation of intratumoral hypoxia with patient survival rate	5 Years	evaluation of correlation of tumoral hypoxia with disease-free survival using Cox proportional hazards analysis

Secondary Outcome Measures

Name	Time	Method
to assess utility of circulating osteopontin and miR-210 for identifying hypoxia	5 Years	correlation of tumoral hypoxic fraction with plasma levels of osteopontin and miR-210
correlation of hypoxia with molecular markers	5 Years	colocalization of molecular markers using immunofluorescence microscopy: Stem-cell like populations markers of EMT Endogenous markers of hypoxia (HIF1a, CAIX)

Trial Locations

Locations (1)

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada