Clinical trial NCT01248637: 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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pancreatic Cancer
Keywords: pancreas
pancreatic cancer
pancreatic tumor
pimonidazole
hypoxia
whipple's resection
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2010-11-25
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participating in ICGC Pancreatic Cancer Genome Project.

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.

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)

Primary outcomes:
measure: characterization of intratumoral hypoxia in pancreatic cancer
timeFrame: 5 Years
measure: correlation of intratumoral hypoxia with patient survival rate
timeFrame: 5 Years
Secondary outcomes:
measure: correlation of hypoxia with molecular markers
timeFrame: 5 Years
measure: to assess utility of circulating osteopontin and miR-210 for identifying hypoxia
timeFrame: 5 Years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Univeristy Health Network - Princess Margaret Cancer Centre
name: Neesha Dhani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.