Study of Intratumoral Hypoxia Using Pre-operative Administration of Pimonidazole

NCT ID: NCT01248637

Last Updated: 2018-07-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2017-12-31

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.

Conditions

Pancreatic Cancer

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: OTHER

Study Groups

Pimonidazole hydrochloride

Oral pimonidazole is administered at a dose of 0.5gm/m2 once approximately 24 hrs prior to surgery

Pimonidazole hydrochloride

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Hypoxyprobe-1

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Neesha Dhani, MD

Role: PRINCIPAL_INVESTIGATOR

Univeristy Health Network - Princess Margaret Cancer Centre

Locations

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 26325106 (View on PubMed)

Other Identifiers

UHN REB 10-0350-C

Identifier Type: -

Identifier Source: secondary_id

PIMO-PANC

Identifier Type: -

Identifier Source: org_study_id