Clinical Trials

The purpose of the study is to compare any inherited or genetic characteristics using blood or tissue specimens collected from individuals who have been diagnosed with lung cancer with the blood or tissue of their family members. The research study is funded by the National Cancer Institute and is part of a national research study being conducted by the Genetic Epidemiology of Lung Cancer Consortium (GELCC).

Blood samples are obtained from those patients undergoing procedures to determine if a lung nodule is benign or cancerous. The data from the study will not be used to guide or influence the treatment of the patients enrolled in this study. There is no change from the normal standard of care that patients receive.

Patients must present with previously non-diagnosted lung nodules as found on CT. There is no change to the typical standard of care that any of the investigating physicians and/or centers provide the patients enrolled in this study. The data from this study will not be used to diagnose cancer nor be used to influence treatment decisions for the study participants.

OBJECTIVES: Primary - To determine whether administering high-dose thoracic radiotherapy, 70 Gy (2 Gy once daily over 7 weeks) or 61.2 Gy (1.8 Gy once daily for 16 days followed by 1.8 Gy twice daily for 9 days), will improve median and 2-year survival compared with 45 Gy (1.5 Gy twice daily over 3 weeks) in patients with limited-stage small cell lung cancer. Secondary - To compare treatment-related toxic effects of thoracic radiotherapy regimens in patients with limited-stage small cell lung cancer. - To compare response rates, failure-free survival, and toxicity of thoracic radiotherapy regimens in patients with limited-stage small cell lung cancer. - To compare rates of local relapse, distant metastases, and brain metastases with these regimens. - To describe the patterns of use of thoracic intensity-modulated radiotherapy (IMRT) in patients with limited-stage small cell lung cancer. OUTLINE: This is a 2-part, multicenter, randomized study. Patients are stratified according to gender, weight loss 6 months prior to study entry (≤ 5% of body weight vs > 5% of body weight), ECOG performance status (0 vs 1 vs 2), radiotherapy technique (intensity-modulated radiotherapy vs 3-dimensional conformal radiotherapy), and radiotherapy start time (at first course of protocol chemotherapy, after one course of prior non-protocol chemotherapy vs at first course of protocol chemotherapy, without prior non-protocol chemotherapy vs at second course of protocol chemotherapy, without prior non-protocol chemotherapy). - Part 1: Patients are randomized to 1 of 3 treatment arms. - Arm I: Patients undergo standard-dose (45 Gy given in 30 treatments) thoracic radiotherapy twice daily, 5 days a week, for 3 weeks. Patients also receive cisplatin IV on day 1 and etoposide IV on days 1, 2, and 3. - Arm II: Patients undergo higher-dose (70 Gy given in 35 treatments) thoracic radiotherapy once daily, 5 days a week, for 7 weeks. Patients also receive cisplatin and etoposide as in arm I. - Arm III: (discontinued as of 03/10/13) Patients undergo higher-dose (61.2 Gy given in 34 treatments) thoracic radiotherapy once daily, 5 days a week, during the initial 16 days (approximately 3 weeks) of treatment and then twice daily, 5 days a week, for the final 9 days (approximately 2 weeks) of treatment. Patients also receive cisplatin and etoposide as in arm I. In all arms, treatment with cisplatin and etoposide repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. - Part 2: An interim analysis was conducted after accrual of 30 patients per arm and one experimental arm based upon a comparison of treatment-related toxicity was selected. The most toxic experimental arm was discontinued, and the trial continues comparing standard therapy (arm I) to the selected experimental regimen (arm II) as described in part 1. Prophylactic radiotherapy: Within 3-6 weeks after completion of chemotherapy, patients with responding disease are eligible to undergo prophylactic radiotherapy to the brain once a day, 5 days a week, for 2 weeks. After completion of study treatment, patients are followed up at least every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years or until disease progression. At disease progression, patients are followed up every 6 months.

PRIMARY OBJECTIVES:  I. To determine the progression-free survival of erlotinib (erlotinib) and bevacizumab versus that of erlotinib alone for the purpose of deciding if the combination arm is worth pursuing in a phase III trial.  SECONDARY OBJECTIVES:  I. To investigate the overall survival of erlotinib and bevacizumab versus erlotinib alone. II. To investigate the response rate of erlotinib and bevacizumab versus erlotinib alone. III. To investigate the progression-free survival in patients with exon deletion 19 or exon 21 L858R EGFR point mutations. IV. To investigate the toxicity of erlotinib and bevacizumab versus erlotinib alone using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. TERTIARY OBJECTIVES:  I. To correlate EGFR mutations detected in plasma deoxyribonucleic acid (DNA) with those detected in tumor DNA. II. To estimate the prevalence of EGFR T790M resistance mutations from pretreatment tumor biopsies using more sensitive mutation detection methods. III. To investigate progression free survival of EGFR mutant NSCLC patients with and without concurrent EGFR T790M detected from pre-treatment tumor specimen using allele specific quantitative polymerase chain reaction (PCR). IV. To prospectively evaluate the predictive value of plasma vascular endothelial growth factor A (VEGF-A) levels on progression free survival in patients treated with erlotinib alone or in combination with bevacizumab.  OUTLINE: Patients are randomized to 1 of 2 treatment arms.   ARM A: Patients receive erlotinib orally (PO) once daily (QD) on days 1-21.  ARM B: Patients receive erlotinib as in Arm A and bevacizumab intravenously (IV) over 30-90 minutes on day 1.   In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.  After completion of study treatment, patients are followed up periodically for up to 5 years.

Patients will be identified and enrolled from Thoracic Surgical Clinics. A preoperative bronchoscopy will be performed to obtain systematic bronchial biopsies from defined proximal airway sites. Patients will then undergo surgical resection and tumor tissue and normal lung specimens collected. For patients with bronchial dysplasia postoperatively, starting less than 90 days from the time of surgery, patients will be randomized to receive either 850 mg po BID of metformin or observation. Metformin dosing will include a 4 week ramp up of 850 mg po daily prior to starting the BID dose. Adjuvant platinum-based chemotherapy will be applied at the discretion of treating physicians.  Patients found to have bronchial dysplasia at the time of bronchoscopy will undergo follow up bronchoscopy and tissue sampling at 6 months follow up.

OBJECTIVES:

     Primary

       -  To determine if maintenance therapy with pemetrexed disodium versus observation improves progression-free survival of patients with malignant pleural mesothelioma who have at least stable disease after completion of first-line therapy comprising pemetrexed disodium with cisplatin or carboplatin.

     Secondary

       -  To determine the overall survival of patients treated with this regimen versus observation.

       -  To evaluate the frequency of responses in patients treated with this regimen.

       -  To assess the toxicity of this regimen in these patients.

     OUTLINE: This is a multicenter study. Patients are stratified according to first-line chemotherapy regimen (cisplatin/pemetrexed disodium vs carboplatin/pemetrexed disodium), histologic subtype (epithelioid vs other) and number of courses received (< 6 vs 6).

       -  Arm I: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

       -  Arm II: Patients undergo observation until disease progression. After completion of study therapy, patients are followed up every 6 months for 3 years.

PRIMARY OBJECTIVES:

     Maximum tolerated dose (MTD) for the intrapleural administration of a modified vaccine strain measles virus (MV) genetically engineered to produce human thyroidal sodium iodine symporter (NIS) (MV-NIS [oncolytic measles virus encoding thyroidal sodium iodide symporter])in patients with MPM.

     SECONDARY OBJECTIVES:

     Safety and toxicity of the repeated (up to 6 cycles) intrapleural administration of MV-NIS in patients with malignant pleural mesothelioma.

     TERTIARY OBJECTIVES:

     I. Time course of viral infection, dissemination and elimination by non-invasive measurements of NIS gene expression using radioactive iodine and single-photon emission computed tomography (SPECT)/ computed tomography (CT) imaging with.

     II. Viremia, viral replication, and viral shedding following intrapleural administration.

     III. Changes in humoral and cellular anti-MV immunity following the intrapleural administration of MV-NIS.

     IV. Antitumor efficacy of this approach by serial measurements of radioiodine uptake by SPECT/CT, radiographic response, and time to disease progression.

     V. Changes in both local and systemic innate and adaptive anti-tumor immunity following the intrapleural administration of MV-NIS.

     VI. Effect of MV-NIS administration on the eukaryotic initiation factor (eIF) 4F translation complex in mesothelioma cells.

     OUTLINE: This is a dose-escalation study.

     Patients receive the oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) intrapleurally. In the absence of unacceptable side effects or disease progression treatment can be repeated every 28 days for up to 6 courses.

     After completion of study treatment, patients are followed up every 3 to 6 months for up to 5 years.

Mesothelioma is a cancer that develops from serosal surfaces usually in response to prior asbestos exposure. A history of asbestos exposure can be elicited in more than 80% of mesothelioma victims. However, asbestos exposure alone is not sufficient to cause the development of mesothelioma. Nearly 27 million individuals in the US, were exposed to asbestos in the work place between 1940 and 1979 but just 3,000 new cases of mesothelioma are diagnosed each year. Therefore, the investigators hypothesis is that genetic variation in addition to asbestos exposure, and host factors contribute to the development of mesothelioma. It is estimated, based on the investigators preliminary studies, that a population in excess of 1,000 subjects with mesothelioma is required to perform a valid GWAS. Therefore a multicenter approach is necessary to collect data and DNA on sufficient numbers with mesothelioma to adequately evaluate genetic risk. It is the aim of this proposal to develop a consortium of mesothelioma investigators to share phenotypic data and DNA samples and to perform genome wide association scanning (GWAS).

The current standard of care for Stage I Non-Small Lung Cancer (NSCLC) is sublobar surgical resection. Recent trials have suggested that early stage NSCLC might be successfully treated with SBRT amongst those who are medically inoperable. SBRT is the precise delivery of a high dose of radiation to control tumors while limiting damage to surrounding normal tissues. Patients on the SBRT arm will receive 54 Grays (Gy) in 3 fractions. One gray is the absorption of one joule of energy, in the form of ionizing radiation, per kilogram of matter. Recent advances with three-dimensional conformal and Intensity Modulated Radiotherapy (IMRT) techniques can now compensate for lung motion and allow delivery of high-dose, single fractions to the primary lung tumor for patients with clinical state I NSCLC.

     Local control and survival results appear promising. SBRT for early stage lung cancer may offer a potentially equivalent, non-invasive treatment alternative to surgical resection. Additionally, SBRT may be associated with fewer complications and better quality of life. SBRT may be an acceptable or even preferred treatment option in higher-risk patients not able to tolerate a surgical lobectomy. This clinical dilemma is increasingly faced in our lung cancer practice at Mayo Clinic, with no comparative effectiveness data to guide treatment decisions.

     Patients will be evaluated by both Thoracic Surgery and Radiation Oncology.  Randomization can occur through either group but a patient must see both in consultation prior to randomization. For patients meeting enrollment criteria but unwilling to participate in randomization, observational arms for each of SBRT and sublobar resection will enroll up to 24 patients as part of the 96 patient total.

     The patients will receive the following tests:

       -  Computed Tomography (CT)-Positron Emission Tomography (PET) will be used for mediastinal imaging

       -  Endobronchial/endoscopic ultrasound (EBUS/EUS)-Fine Needle Aspiration (FNA) or mediastinoscopy will be used for pathologic assessment of level 2 lymph nodes (N2) greater than 1 cm in the short axis on CT scan and/or SUV greater than 1.5 fold background

       -  Follow-up CT every 3 months for 2 years for SBRT groups, with triggers for further evaluation

       -  Baseline CT scan at 3 months for surgery groups, then yearly afterwards

       -  Follow-up Pulmonary Function Tests at 1 year