An Analysis Of The Response Of Human Tumor Microvascular Endothelium To Ionizing Radiation

Study Overview

An Analysis of the Response of Human Tumor Microvascular Endothelium to Ionizing Radiation

Doctors will take some tissue from the tissue removed during surgery in order to study how the blood vessels of the tumor respond to radiation therapy. The tissue obtained will be used to determine how these tumor blood vessels respond to radiation therapy delivered to the tumor, after it has been removed. This radiation is delivered in the research lab. This research is being conducted in order to develop new methods to treat tumors by radiation therapy. No additional surgery will be performed to obtain these samples, and only materials that remain after all diagnostic testing has been completed will be used.

The goal of this study is to determine if concepts established in mouse models of the tumor microvascular response to ionizing radiation (IR) therapy are applicable to human tumors in order to begin to establish that the engagement of the endothelial response is a valid target for IR in human tumors. A portion of tumor will be isolated from individuals who have signed informed consent for this protocol and are undergoing surgery on the Neurosurgery, Colorectal, and Gynecology, Head and Neck, Urology, and Hepatobiliary Services at Memorial Sloan-Kettering Cancer Center. Tumor tissue will be obtained from the surgical sample in pathology after adequate specimens have been obtained for diagnostic purposes. Tumor tissue will be irradiated ex vivo and the microvascular endothelial response will be determined. From specimens of adequate size, a pure tumor endothelial cell population will be isolated and the response to IR will be determined. Primary Outcomes: * To determine if human tumor microvascular endothelium displays similar dose parameters as mouse tumor endothelium. Secondary Outcomes: * To determine if tumor endothelium isolated to near homogeneity demonstrates dose parameters similar to those used in single dose radiotherapy of brain tumors. * To determine if the microvascular endothelium of tumors of different types behaves in a similar fashion in its response to IR.

Ovarian Neoplasms
Colorectal Neoplasms
Melanoma
Small Cell Lung Cancer
Liposarcoma

RADIATION: Ionizing radiation (IR) therapy
RADIATION: Ionizing radiation (IR)

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Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2005-08-18	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2014-07-23
First Submitted that Met QC Criteria 2005-08-19	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2014-07-24
First Posted (ESTIMATED) 2005-08-22	Results First Posted N/A	Last Verified 2014-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
N/A

Allocation:
N/A

Interventional Model:
N/A

Masking:
N/A

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
: A The experiments in Group A will be conducted in order to determine if human tumor microvascular endothelium displays similar dose parameters as mouse tumor endothelium, and if the microvascular endothelium of tumors of different types behaves in a similar	RADIATION: Ionizing radiation (IR) therapy Tumors will be sliced into 0.5cm fragments, incubated in culture medium and then irradiated to evaluate the kinetics and dose-dependencies of the endothelial apoptotic response. We will irradiate tumor fragments ex vivo at 0, 7, 13, 15, 17, and 25 Gy.
: B The experiments in Group B will be conducted in order to determine if tumor endothelium isolated to near homogeneity demonstrates dose parameters similar to those used in single dose radiotherapy of brain tumors.	RADIATION: Ionizing radiation (IR) Tissue fragments of a total quantity of at least a 4x4x4 cm3 will be required. For each tumor a paraffin block will also be made for routine staining and IHC. Endothelial cell populations (at least 500 cells) will then be exposed to radiation at 0, 7, 11,

Participant Group/Arm

Intervention/Treatment

: A

The experiments in Group A will be conducted in order to determine if human tumor microvascular endothelium displays similar dose parameters as mouse tumor endothelium, and if the microvascular endothelium of tumors of different types behaves in a similar

RADIATION: Ionizing radiation (IR) therapy

Tumors will be sliced into 0.5cm fragments, incubated in culture medium and then irradiated to evaluate the kinetics and dose-dependencies of the endothelial apoptotic response. We will irradiate tumor fragments ex vivo at 0, 7, 13, 15, 17, and 25 Gy.

: B

The experiments in Group B will be conducted in order to determine if tumor endothelium isolated to near homogeneity demonstrates dose parameters similar to those used in single dose radiotherapy of brain tumors.

RADIATION: Ionizing radiation (IR)

Tissue fragments of a total quantity of at least a 4x4x4 cm3 will be required. For each tumor a paraffin block will also be made for routine staining and IHC. Endothelial cell populations (at least 500 cells) will then be exposed to radiation at 0, 7, 11,

Primary Outcome Measures	Measure Description	Time Frame
apoptotic response	The peak apoptotic radiation response will be obtained for each of the tumor type and the result compared to that of the mouse experiments in Garcia-Barros (no formal testing only qualitative statements).	2 years

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
19 Years

Accepts Healthy Volunteers:

Patients who are felt to have adequate tumor volume for these studies, at least a 2 x 2 x 2 cm3 tumor by physical exam, imaging studies or colonoscopy reports
Primary or recurrent tumors are eligible
Patients must be suitable candidates for surgery
Patients who have signed the informed consent

Patients who are not considered suitable candidates for surgery
Patients who have received prior radiation therapy to the tumor being removed
Patients who have received chemotherapy within 6 months of tumor removal
Patients who are pregnant
Patients may choose to be excluded at any time
Minors are excluded from this study because there are expected to be very few minors with the tumor types which the investigators are evaluating in this study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Michael Zelefsky, M.D., Memorial Sloan Kettering Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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