Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Lung Neoplasms

Neoplasm Metastasis

Esophageal Neoplasms

Mesothelioma

Mesothelioma, Malignant

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Pleural Neoplasms

Esophageal Cancer

Malignant Mesothelioma

Subjects with potentially malignant or suspicious lesions, or biopsy proven thoracic cancers or thoracic metastases from cancers of non-thoracic origin

Deneise Francis, R.N.

David S Schrump, M.D.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

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 2 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. Note: Patients \>= 2 years of age and under 18 years of age may only participate in research sample collection.

Design:

* Up to 1100 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.

Background:

* Lung and esophageal cancers as well as malignant pleural mesotheliomas exhibit epigenetic perturbations that 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, longitudinal manner.

Objectives:

* To permit evaluation of patients referred to the Thoracic Surgery Branch, NCI in order to identify individuals who will be suitable candidates for clinical research protocols.
* To obtain 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 Branch.
* To perform focused germline testing of genes modulating drug metabolism, possible future whole genome sequencing studies, possible 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 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 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.
* Age \>= 2 years and older. Note: Patients \>= 2 years of age and under 18 years of age may only participate in research sample collection if the tissue acquisition is performed during a clinically indicated surgical procedure, and the sampling of tissue, blood or urine does not add risk to the clinically indicated procedures.

Design:

* This protocol is designed to:
* Facilitate screening of patients for investigational protocols in the Thoracic Surgery Branch, NCI, and to 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 Epigenetics 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 standard staging, surgical intervention, and follow up care. Tissue, blood, and/or peritoneal/pleural effusion samples obtained during surgery/biopsy or clinic visits 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 may 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 undergo standard of care treatment at the NIH Clinical Center on this study.
* It is anticipated that the protocol will enroll a maximum of 1310 patients.

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

Prospective Evaluation of Genetic and Epigenetic Alterations in Patients With Thoracic Malignancies

.All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

evaluation of patients referred to the Thoracic Surgery Branch, NCI in order to identify individuals who will be suitable candidates for treatment/intervention research protocols

National Cancer Institute (NCI)

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Squamous Cell

Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Nivolumab 240 mg fixed dose IV every 2 weeks; Additionally, after 7 week safety assessment Ipilimumab 1mg/kg IV every 6 weeks

Nivolumab 240 mg fixed dose IV every 2 weeks

Nivolumab 240 mg IV fixed dose every two weeks

Ipilimumab 1mg/kg IV every six weeks (starting in week 7 after safety assessment)

Matthias Ebert, Prof. Dr.

Cancer - including esophageal squamous cell cancer (ESCC) - is a disease of the elderly but little is known about the biology and progression of cancers in these patients.

While most patients receive chemotherapy and/or chemo-radiation as first treatment, no treatment standard for following treatments has been established so far and there is a clear unmet medical need, especially for elderly patients.

Hence, this study assesses the efficacy and safety of two experimental immunotherapy regimens (Nivolumab monotherapy or Nivolumab/Ipilimumab combination) in elderly patients with advanced esophageal squamous cell cancer.

Cancer - including esophageal squamous cell cancer (ESCC) - is a disease of the elderly, more than 60% of all tumors arise in patients with the age of 65 years or older. In contrast, little is known about the biology and progression of cancers in these patients, since most clinical trials enroll patients with age limits of 70 or 75 years.

While most patients undergo chemotherapy and/or chemo-radiation in first-line, the role of second-line therapy is less well understood. No treatment standard has been established so far and there is a clear unmet medical need. This is particularly true for geriatric patients for whom palliative systemic therapies are especially challenging.

Hence, the primary objective of this trial is to demonstrate a significant survival benefit of two experimental immunotherapy regimens (Nivolumab monotherapy or Nivolumab/Ipilimumab combination) in elderly patients with advanced esophageal squamous cell cancer compared to historical data of standard chemotherapy regimens.

A Multicenter Open-label Phase II Trial to Evaluate Nivolumab and Ipilimumab for 2nd Line Therapy in Elderly Patients With Advanced Esophageal Squamous Cell Cancer

OS measured from first dose of 2nd line therapy to the date of death

Time to QoL deterioration defined as a loss of ≥ 10 points in the EORTC QLQ-C30 compared to base-line

Time from first dosing date to the date of the first documented tumor progression

Proportion of treated subjects with response from baseline

Time from first confirmed response to the date of the documented progressive disease or death

Time from date of first dose of Nivolumab monotherapy until permanent discontinuation of either NIVO mono therapy or NIVO/IPI combination treatment.

EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire (30 items) Version 3.0. The QLQ-C30 is composed of multi-item scales and single-item measures, including five functional scales, three symptom scales, a global health status / QoL scale, and six single items.

All of the scales and single-item measures have a score range from 0 to 100. A high score shows a high response level. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems

EORTC QLQ-ELD14 (European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire Module for elderly Cancer patients (14 items), comprising five multi-item and two single-item subscales. The multi-item subscales include questions about mobility (3 items), worries about others (2 items), worries (3 items), maintaining purpose (2 items), and burden of illness (2 items). The single-item subscales include questions related to joint stiffness and Family support. Items are assessed on a 4-level numerical scale with 1= "not at all", 2= "a little", 3= "quite a bit", and 4= "very much". Scores are linearly converted and summated into a scaled score from 0 to 100, with a higher score representing a worse QOL or better QOL for purpose and family support.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Cell Changes in Blood and Tissue in Cancers of the Lung, Esophagus and Lung Lining	NCT00242723	Malignant Pleur... Esophageal Canc... Lung Cancer NOS Thoracic Cancer... Cancers of Non ...		2 Years -	National Institutes of Health Clinical Center (CC)
A Multicenter Open-label Phase II Trial to Evaluate Nivolumab and Ipilimumab for 2nd Line Therapy in Elderly Patients With Advanced Esophageal Squamous Cell Cancer	NCT03416244	Esophageal Canc... Oesophageal Can... Oesophageal Can... Esophageal Canc... Esophageal Canc... Oesophageal Can... GastroEsophagea... Gastrooesophage...	Nivolumab Ipilimumab	65 Years -	AIO-Studien-gGmbH
A Multicenter Open-label Phase II Trial to Evaluate Nivolumab and Ipilimumab for 2nd Line Therapy in Elderly Patients With Advanced Esophageal Squamous Cell Cancer	NCT03416244	Esophageal Canc... Oesophageal Can... Oesophageal Can... Esophageal Canc... Esophageal Canc... Oesophageal Can... GastroEsophagea... Gastrooesophage...	Nivolumab Ipilimumab	65 Years -	AIO-Studien-gGmbH

Spots Global Cancer Trial Database for esophageal cancers nos