Molecular Analysis of Thoracic Malignancies

• ClinicalTrials.gov Identifier: NCT01385722
• Recruitment Status: Enrolling by invitation
• First Posted: June 30, 2011
• Last Update Posted: June 14, 2022
• Sponsor: Stanford University
• Information provided by (Responsible Party): Stanford University

Tracking Information

• First Submitted Date: June 28, 2011
• First Posted Date: June 30, 2011
• Last Update Posted Date: June 14, 2022
• Study Start Date: August 2011
• Estimated Primary Completion Date: June 2031 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 29, 2011): Collect detailed clinical information on patients with thoracic malignancies via the electronic medical record and a detailed patient questionnaire [ Time Frame: 20 years ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Molecular Analysis of Thoracic Malignancies
• Official Title: Molecular Analysis of Thoracic Malignancies
• Brief Summary: 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.

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.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

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.

• 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.

Condition

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

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: June 29, 2011): 1000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2031
• Estimated Primary Completion Date: June 2031 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01385722
• Other Study ID Numbers: IRB-21319; SU-06232011-7986 ( Other Identifier: Stanford University ); THOR0004 ( Other Identifier: OnCore )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Stanford University
• Original Responsible Party: Joel Neal, Stanford University School of Medicine
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Joel Neal; Stanford University

• PRS Account: Stanford University
• Verification Date: June 2022