Trial Information

Prospective Evaluation of Epigenetic Alterations in Patients With Thoracic Malignancies

BACKGROUND:

- Lung and esophageal cancers as well as malignant pleural mesotheliomas exhibit profound
alterations in chromatin structure, which may impact the clinical course of these
neoplasms.

- To date, epigenetic alterations in primary thoracic malignancies and neoplasms
metastatic to the chest have not been evaluated in a systematic manner.

OBJECTIVES:

- To permit evaluation of patients referred to the Thoracic Oncology Section, Surgery
Branch, NCI in order to identify individuals who will be suitable candidates for
clinical research protocols.

- To obtain biopsies during staging studies of tumor and adjacent normal tissues as well
as serum and urine samples from patients with primary or metastatic malignancies
involving the lung, esophagus, pleura, and mediastinum to support preclinical research
endeavors in the Thoracic Oncology Section.

- To obtain blood, tumor tissue or malignant peritoneal/pleural effusions from patients
with lung, esophageal, mediastinal, or chest wall malignancies for ex vivo generation
of autologous tumor cell lines and EBV-transformed B cell lines for research. Tumor
tissue obtained during previous protocol participation and cryopreserved may undergo
this process if the patient consents on this trial.

- To permit standard treatment for patients who are not eligible for investigational
therapy on a current Thoracic Oncology protocol, but who present a novel and unique
clinical training opportunity, or who manifest a clinical condition that requires
immediate intervention to prevent compromise to the patient's well-being.

- To permit long term follow up of patients with thoracic malignancies including the
collection of tissue and fluids to support preclinical research particularly to
ascertain if gene expression and DNA methylation profiles coincide with response to
therapy.

ELIGIBILITY:

- Patients with potentially malignant or suspicious lesions or with biopsy proven, lung
cancers or esophageal cancers, malignant pleural mesotheliomas, mediastinal or chest
wall neoplasms, thymoma/thymic neoplasms, or pulmonary metastases from cancers of
non-thoracic origin.

- Patients who have an ECOG performance score of 0-2.

- Patients under 18 years of age may participate if the tissue acquisition is performed
during a clinically indicated surgical procedure, and the sampling of tissue, blood and
urine does not add risk to the clinically indicated procedures.

- Patients must have coagulation parameters within acceptable limits by standard of
practice guidelines prior to biopsy

DESIGN:

- This protocol is designed to:

- facilitate screening of patients for investigational protocols in the Thoracic
Oncology Section, Surgery Branch, NCI, and in doing so, obtain tissue samples to
enable evaluation of epigenetic events in primary and metastatic thoracic
malignancies, as an extension of ongoing laboratory research in the Thoracic
Oncology laboratory.

- allow for the establishment of tumor cell lines and EBV-transformed B cell lines
to support immunologic evaluation of the patient's response to other clinical
trials.

- Patients will be screened to determine appropriate diagnostic and treatment
interventions. Where appropriate, patients will receive staging and surgical
intervention and necessary follow up care. Tissue, blood, and/or peritoneal/pleural
effusion samples obtained during surgery/biopsy or clinic visit will be processed and
either stored for analysis or cultured for generation of tumor cell lines and
EBV-transformed B cell lines for research. After recovery from biopsy or surgery
patients will continue to be followed, blood and urine samples will be collected as
well as tissue when appropriate.

- No investigational treatment will be administered on this protocol. In circumstances
approved by the Section Chief, a patient may be deemed ineligible for investigational
therapy, yet may present a unique clinical training experience for Thoracic Oncology
Section physicians and clinical associates, and undergo standard treatment.

- It is anticipated that the protocol will enroll 75 patients per year over 5 years for a
total of 375 patients.