An Analysis of the Response of Human Tumor Microvascular Endothelium to Ionizing Radiation - Full Text View

Purpose

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.

Condition	Intervention	Phase
Ovarian Neoplasms Colorectal Neoplasms Melanoma Small Cell Lung Cancer Liposarcoma	Radiation: Ionizing radiation (IR) therapy Radiation: Ionizing radiation (IR)	Phase III

Genetics Home Reference related topics:

breast cancer

MedlinePlus related topics:

Cancer Colorectal Cancer Lung Cancer Melanoma Ovarian Cancer

Drug Information available for:

Radiation, ionizing Paraffin

U.S. FDA Resources

Study Type:	Observational
Study Design:	Cohort, Prospective

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

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Biospecimen Retention: Samples With DNA

Biospecimen Description:

tissue

Estimated Enrollment:	150
Study Start Date:	August 2004
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
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 fashion in its response to IR.	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, 13, 15, 17, and 25 Gy and harvested at 4, 5 and 8 hours post IR.

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	19 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

undergoing surgery on the Neurosurgery, Hepatobiliary, Colorectal, Urology, Head and Neck, Gynecology, GMT and Thoracic Services at Memorial Sloan- Kettering Cancer Center.

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00132704

Contacts


Contact: Michael Zelefsky, M.D.	212-639-6802	zelefskm@mskcc.org

Contact: James Eastham, MD		easthamj@mskcc.org

Locations


United States, New York
	Memorial Sloan-Kettering Cancer Center	Recruiting
	New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Michael Zelefsky, M.D.	Memorial Sloan-Kettering Cancer Center

More Information

(Memorial Sloan-Kettering Cancer Center) This link exits the ClinicalTrials.gov site

Responsible Party:	Memorial Sloan Kettering Cancer Center ( Michael Zelefsky, MD )
Study ID Numbers:	04-109
First Received:	August 18, 2005
Last Updated:	November 6, 2008
ClinicalTrials.gov Identifier:	NCT00132704
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Lung cancer metastases to the CNS (adenocarcinomas)

Melanoma metastases to the CNS

Breast cancer metastases to the CNS (ductal carcinomas)

Central nervous system gliomas

Colorectal cancers (adenocarcinomas)

Ovarian cancers (papillary serous carcinomas)

Endometrial cancers (endometrioid carcinomas)

Cervical cancers (squamous cell carcinomas)

Sarcomas (liposarcomas and leiomyosarcomas)

Thoracic mesotheliomas

Colorectal cancers metastatic to the liver

Primary adenocarcinomas of the lung

Primary squamous cell carcinomas of the lung

Pancreatic Cancers-adenocarcinoma

Study placed in the following topic categories:

Thoracic Neoplasms

Pancreatic Neoplasms

Malignant mesenchymal tumor

Colonic Diseases

Urogenital Neoplasms

Carcinoma, Endometrioid

Rectal Diseases

Neoplasms, Connective and Soft Tissue

Lung Neoplasms

Neoplasm Metastasis

Neuroepithelioma

Glioma

Endocrine Gland Neoplasms

Digestive System Neoplasms

Genital Neoplasms, Female

Breast Neoplasms

Endocrine System Diseases

Carcinoma

Carcinoma, Small Cell

Neuroectodermal Tumors

Liposarcoma

Lung Diseases

Sarcoma

Gastrointestinal Neoplasms

Nevus

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Cystadenocarcinoma, Serous

Carcinoma, Neuroendocrine

Leiomyosarcoma

Additional relevant MeSH terms:

Respiratory Tract Neoplasms

Neoplasms

Neoplasms by Histologic Type

Neoplasms by Site

Neoplasms, Nerve Tissue

Nevi and Melanomas

Adnexal Diseases

Neoplasms, Adipose Tissue

ClinicalTrials.gov processed this record on November 30, 2008

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00132704