Molecular Analysis of Thoracic Malignancies

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Stanford University
ClinicalTrials.gov Identifier:
NCT01385722
First received: June 28, 2011
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

A research study to learn about the biologic features of cancer development, growth, and spread. We are studying components of blood, tumor tissue, normal tissue, and other fluids, such as urine, cerebrospinal fluid, abdominal or chest fluid in patients with cancer. Our analyses of blood, tissue, and/or fluids may lead to improved diagnosis and treatment of cancer by the identification of markers that predict clinical outcome, markers that predict response to specific therapies, and the identification of targets for new therapies.


Condition
Thymus Cancer
Thymoma
Thymic Carcinoma
Lung Cancer
Carcinoma, Non-Small-Cell Lung
Mesothelioma

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Molecular Analysis of Thoracic Malignancies

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Collect detailed clinical information on patients with thoracic malignancies via the electronic medical record and a detailed patient questionnaire [ Time Frame: 20 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

The potential tumor tissues to be collected include paraffin-embedded tissue, frozen tissues, or fresh tissue. These will be stored in conjunction with the Stanford Tissue Bank.


Estimated Enrollment: 1000
Study Start Date: August 2011
Estimated Study Completion Date: June 2031
Estimated Primary Completion Date: June 2031 (Final data collection date for primary outcome measure)
Detailed Description:

In the United States, an estimated 222,520 lung and bronchus cancers will be diagnosed in 2010, and 157,300 people will die of this disease. Therefore, there is an urgent need for safer and more effective therapies for lung cancer.1 Lung cancer falls into two major classifications, non-small cell lung cancer (NSCLC) which accounts for approximately 87%, and small cell lung cancer (SCLC), which accounts for the remainder. Thymomas are the most common tumors of the anterior mediastinum, and typically occur in adults older than 40 years. While surgical resection and radiation often effectively treat these tumors, a minority continue to progress and eventually lead to death. Thymic carcinomas are a related subset of tumors that more often metastasize and are more aggressive. Finally, mesothelioma often behaves as aggressively as lung cancer, and is not frequently amenable to curative resection.

While the role of molecular alterations has yet to be defined in the treatment of SCLC, thymoma, and mesothelioma, there is an increasing recognition that molecular alterations in NSCLC are important predictors of response to novel targeted therapies. Small molecule tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) signaling pathway, such as erlotinib and gefitinib, improve survival in the second-line treatment of unselected patients with NSCLC. However, retrospective subgroup analysis of these clinical trials has revealed that patients with particular clinical features were more likely to benefit from therapy, such as those with tumors of adenocarcinoma histology, women, Asian ethnicity, and light or never smokers. Conventional Deoxyribonucleic acid (DNA) sequencing of tumors from multiple series of patients that had dramatic responses to gefitinib, as compared with patients without responses, revealed the presence of characteristic genetic mutations in the EGFR gene.4-6 The previously identified clinical markers of response to EGFR TKIs were found to be commonly associated with the presence of these mutations; thus, these clinical features are actually believed to be surrogates for the molecular biomarker of EGFR mutation. Over 90% of EGFR tyrosine kinase domain mutations associated with sensitivity to EGFR Tyrosine kinase inhibitor (TKI) therapy fall into two categories, in-frame deletions in exon 19, and the L858R point mutation in exon 21. These mutations appear to specifically activate both cell proliferation, via activation of the MAP kinase pathway, and survival signals, via activation of the PI3 kinase pathway.7 Therefore, tumors with EGFR mutations are "oncogene addicted" to EGFR survival signals, relying exclusively upon the EGFR signaling cascade to maintain viability, which explains their exquisite sensitivity to TKI therapy. A number of recent large randomized studies have conclusively demonstrated that clinical selection of patients alone is inadequate, and instead establish EGFR mutation status as the single most important predictive marker of response to EGFR-TKI therapy.8-10 In another emerging but similar story, genetic fusion of the anaplastic lymphoma kinase (ALK) tyrosine kinase to a partner protein, EML4, appears to strongly predict sensitivity to the ALK TKI, crizotinib. 11 In addition, there is evidence that less common mutations in NSCLC, such as BRAF mutations and ERBB2 (e.g. HER2) mutations, may also predict response to targeted therapies.

In summary, identification of genetic alterations in NSCLC is increasingly essential for individualizing treatments and performing molecular diagnostics. While the investigators do not anticipate benefits to individual patients, identification of molecular alterations in small cell lung cancer, thymic malignancies, and mesothelioma may provide similar keys to the utilization of novel therapies. This project aims to create a registry of patients and tumors to further the characterization of molecular alterations in thoracic malignancies and develop markers of early detection.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Participants will be identified who come to the Stanford Cancer Center seeking a Thoracic Oncology medical opinion for their disease.

Criteria

Inclusion Criteria:

1.Histologically proven diagnosis of non-small cell lung cancer, small cell lung cancer, thymoma, thymic carcinoma, mesothelioma, or carcinoma of unknown primary consistent with the presentation of a primary thoracic malignancy.

2.18 years of age or older.

3.Ability to understand and the willingness to sign a written informed consent document.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01385722

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Joel Neal Stanford University
  More Information

No publications provided

Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT01385722     History of Changes
Other Study ID Numbers: THOR0004, SU-06232011-7986, 21319
Study First Received: June 28, 2011
Last Updated: July 9, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma
Mesothelioma
Neoplasms, Mesothelial
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenoma
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 01, 2014