Patient case: 52-year-old male with Lung cancer. Genetic variant: EML4-ALK Fusion transcript. Other conditions: Hypertension, Osteoarthritis.

Clinical trial: Evaluation of Cell Changes in Blood and Tissue in Cancers of the Lung, Esophagus and Lung Lining

Summary: Background:
  -  Chromatin is is the structural building block of a chromosome. It is found inside the nucleus of the cell and consists of a complex of DNA and protein.
  -  Cancers of the lung, pleura (lung lining) and esophagus show profound changes in chromatin structure that may affect the course of disease in patients.
  -  A better understanding of these diseases and the genetic changes associated with them may be helpful in developing new treatments for them.
  Objectives:
  -  To evaluate people with cancer of the lung, pleura or esophagus for participation in NCI clinical trials.
  -  To obtain biopsies (small pieces of tissue) from tumor, normal tissue and blood samples to learn more about the cellular changes in blood and tissue in tumors of the lung, esophagus and pleura and surrounding structures in the chest.
  Eligibility: Patients 18 years of age and older with cancer of the lung, esophagus, pleura, mediastinum or chest wall, or cancers of other origin that have invaded the lung.
  Design:
  -  Up to 800 patients may be included in this study.
  -  Patients undergo standard tests for evaluating the stage of their disease and for determining eligibility for an NCI investigational treatment study.
  -  All patients undergo bronchoscopy and bronchoalveolar lavage ("washing" with salt water) to assess their tumor and collect a sample of normal tissue. Patients whose tumor is located on the outside portion of the lung may also undergo thoracoscopy to obtain a tumor sample. For bronchoscopy and bronchoalveolar lavage a tube with a light is passed through the nose or mouth into the lungs to examine the airways. Salt water is injected through the tube and then withdrawn to obtain cells for laboratory studies. For the thoracoscopy a small tube with a light is put through a small hole in the chest to obtain the tumor sample. Both procedures are usually done under general anesthesia. The tissue is examined to identify cell characteristics of people who respond to certain therapies and to identify markers on the surface of the tissue that may be useful in future research and treatment.
  -  Blood and urine samples are collected from patients.
  -  Patients who are eligible for a treatment study at NCI are offered participation in the study.
  -  Patients for whom standard surgery, radiation or chemotherapy is more appropriate may receive treatment at NCI or with their own physician.
  -  Patients who receive treatment at NCI return for follow-up examinations 4 weeks after discharge and then every 2 to 4 months depending on the nature of their cancer.

Detailed description: 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 Surgery Section, of the Thoracic and GI Oncology 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 Surgery Section.
  -  To obtain blood, buccal mucosa, tumor tissue or malignant peritoneal/pleural effusions from patients with lung, esophageal, mediastinal, or chest wall malignancies for focused germline testing of genes modulating drug metabolism, possible future whole genome sequencing studies, possible ex vivo generation of autologous tumor cell lines and EBVtransformed 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 Surgery 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 Surgery Section, of the proposed Thoracic and GI Oncology 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 Surgery Section physicians and clinical associates, and undergo standard treatment.
  -  It is anticipated that the protocol will enroll ~ 75 - 80 patients per year over 10 years for a maximum of 800 patients.

Eligibility: -  INCLUSION CRITERIA:
  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 carcinomas, or thoracic metastases from cancers of non-thoracic origin.
  Patients must have an ECOG performance score of 0-2.
  Patients must be 18 years of age or older. 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 be aware of the neoplastic nature of his/her illness. The patient or parent must be willing to sign an Informed Consent, and undergo endoscopic biopsies of tumor and adjacent normal tissues, and provide blood (30cc) and urine (100cc) samples to support ongoing laboratory research endeavors pertaining to the epigenetics of thoracic malignancies.
  EXCLUSION CRITERIA:
  Candidates who do not meet the inclusion criteria

Relevance to patient case: not relevant