Lung Adenocarcinoma

Brief Summary This prospective, open-label pilot study is designed to evaluate the safety, tolerability, feasibility, and preliminary clinical activity of inhaled cromolyn sodium administered by dry powder inhalation in participants with locally advanced lung cancer. Cromolyn sodium is an FDA-approved mast cell stabilizer with an established safety profile in respiratory disease. Increasing evidence suggests that inflammatory signaling, mast cell activation, and stromal remodeling contribute to tumor progression, immune dysregulation, and resistance to therapy within the lung tumor microenvironment. Modulation of these pathways may represent a novel therapeutic strategy in lung cancer. Approximately 5 to 10 participants with locally advanced lung cancer will receive inhaled cromolyn sodium according to the study protocol. Participants will undergo clinical assessments, safety monitoring, laboratory evaluations, and radiographic imaging in accordance with protocol-defined procedures and standard oncologic care. The primary objective of this pilot study is to evaluate the safety, tolerability, and feasibility of inhaled Cromolyn sodium administration in this patient population. Secondary objectives include exploratory assessment of radiographic response, clinical outcomes, biomarker trends, and potential signals of biological activity. Data generated from this study are intended to support the development of future clinical investigations evaluating the role of mast cell stabilization and tumor microenvironment modulation in lung cancer.

This observational study evaluates if ex-vivo lung cancer drug sensitivity testing results correlate with the driver mutations found by genetic sequencing and if it can predict treatment response.

This randomized clinical trial studies the Beating Lung Cancer in Ohio protocol in improving survival in patients with stage IV non-small cell lung cancer. The Beating Lung Cancer in Ohio protocol may help in evaluating immunotherapies and targeted therapies that prolong survival, have more favorable toxicity profiles than conventional chemotherapy and impact quality of life.

This phase II trial tests whether TRC102 (methoxyamine hydrochloride) in combination usual care treatment comprised of pemetrexed, cisplatin or carboplatin, and radiation therapy followed by durvalumab works better than the usual care treatment alone to shrink tumors in patients with stage III non-squamous non-small cell lung cancer (NSCLC). TRC102 is in a class of drugs called antineoplastic agents. It blocks the ability of a cell to repair damage to its deoxyribonucleic acid (DNA) and may kill tumor cells. It may also help some anticancer drugs work better. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy sources to kill tumor cells and shrink tumors. Giving TRC102 in combination with usual care treatment may be more effective than usual care treatment alone in stabilizing and lengthening survival time in patients with stage III non-squamous NSCLC.

This observational study evaluates whether vortioxetine - an antidepressant medication with cognitive-enhancing properties - can reduce the neurological and cognitive side effects associated with lorlatinib treatment in patients with non-small cell lung cancer (NSCLC) harboring ALK or ROS1 gene rearrangements. Lorlatinib is a highly effective third-generation tyrosine kinase inhibitor, but it causes neuropsychological adverse events (NAEs) in approximately 42% of patients, including cognitive impairment, mood changes, and speech disturbances. Vortioxetine has demonstrated cognitive improvement in depressed patients and in preclinical models of androgen deprivation therapy-induced cognitive impairment. Twenty-four adult patients with ALK/ROS1-positive NSCLC receiving lorlatinib as standard care and prescribed vortioxetine (10-20 mg/day) for NAE management will be enrolled. Comprehensive neuropsychological assessments and quality-of-life questionnaires will be conducted at baseline, week 6, week 12, and month 6 to document changes in cognitive function, depressive symptoms, and quality of life.

This research is designed to determine if experimental treatment with Antibody-drug conjugate, AZD5335, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced tumors

Lung cancer remains a significant challenge in oncology, with poor prognosis for patients, especially those with advanced-stage disease. The phenomenon of tumor spread through air spaces (STAS) in pulmonary cancer has garnered attention for its association with aggressive tumor behavior and adverse clinical outcomes. Spread through air spaces identification has been highly debatable on scientific community as an important prognostic feature for distant and locoregional recurrence and as a key player in the differential diagnosis and selection of the appropriate treatment. The aim of this study is to unravel the complexities of STAS-positive lung adenocarcinoma (LUAD) diagnosis and treatment options. For that, we intend to (1) isolate primary lung cancer tissues from early-stages lung adenocarcinoma to fabricate organoid in vitro models and (2) evaluate the microRNA (miRNA) profile of tumor and healthy tissue samples. This is a Hybrid (prospective and retrospective) observational clinical study with a nested translational study.

The project aims to perform integrated PET/MR or PET/CT visualization of patients with clinically suspected or confirmed pancreatic cancer, ovarian cancer, lung adenocarcinoma and other malignant tumors with high MSLN expression and healthy volunteers, using targeted MSLN-specific imaging agents (taking \[68Ga\]Ga-NOTA-MSLN antibody fragment as an example), to achieve the following purposes: Patients with malignant tumors: for diagnosis and staging of diseases, comparing with the gold standard pathological diagnosis, evaluating diagnostic efficacy, clarifying the presence or absence of lesions, and determining the location and nature of lesions; comparing with \[18F\]FDG PET for accurate staging, evaluating the tumor load, and helping to determine the therapeutic plan. Healthy volunteers: Pharmacokinetic analysis will be performed to clarify the distribution and metabolism of the drug in the body and its safety.

This is an open label, phase II study to assess the efficacy of osimertinib (80 mg, orally, once daily) to suppress the progression of remaining GGN(s) in other lobes following surgical resection for actionable EGFR mutation-positive stage IB-IIIA lung adenocarcinoma.

The objective of this study is to develop a Decision Aid for Lung Cancer Molecular Testing (DA\_LCMT) and to facilitate shared-decision making in patients who were diagnosed with lung adenocarcinoma by intraoperative frozen pathology about whether to conduct the molecular testing.

The goal of this observational study is to describe the prevalence of germ line-pathogenic variants in Mexican patients with lung adenocarcinoma. The main questions it aims to answer are: 1. What is the prevalence of pathogenic variants in genes associated with lung adenocarcinoma in Mexican patients younger than fifty? 2. Which clinical-pathological characteristics are associated with germ-line pathogenic variants in patients with lung adenocarcinoma? 3. How actionable somatic mutations are associated with germ line-pathogenic variants of patients with lung adenocarcinoma? Participants will be asked to sign an informed consent; after that, they will be instructed to donate 10 ml of peripheral blood by venipuncture in the morning and before the patient has taken morning medication and the first meal, following a period of 8-12 hr fasting.

This study aims to evaluate the non-inferiority in recurrence-free survival and overall survival of segmentectomy compared with lobectomy in patients with lung adenocarcinoma ≤ 2 cm with micropapillary and solid subtype negative by intraoperative frozen sections.

This is a phase 3, randomized, controlled clinical trial comparing two brain-directed treatment strategies for adult patients with extensive brain metastases from lung adenocarcinoma. The trial compares fractionated stereotactic radiotherapy combined with bevacizumab (FSRT-Bev) versus hippocampus-avoidant whole-brain radiotherapy with simultaneous integrated boost (HA-WBRT-SIB). The main objectives are to evaluate intracranial tumor control and preservation of neurocognitive function . Patients will be randomly assigned in a 1:1 ratio to receive either FSRT plus bevacizumab or HA-WBRT-SIB. In the experimental group, FSRT is delivered to visible brain tumors over 5 daily treatments (total 30 Gy, 6 Gy per fraction). Bevacizumab is given intravenously every 3 weeks for 4 cycles. In the control group, patients receive hippocampus-avoidant whole-brain radiation (25 Gy) with a simultaneous dose boost to metastatic lesions (40 Gy total) over 10 daily treatments.

This study evaluates whether a 7-day ketogenic dietary regimen before 2-\[18F\]FDG PET/CT can improve the diagnostic accuracy of imaging in adults with suspected or histologically confirmed lepidic-predominant lung adenocarcinoma (LPA). LPA frequently shows low glucose metabolism and may yield false-negative FDG PET/CT results. Approximately 30 participants will undergo a tailored ketogenic diet for 7 days before PET/CT. Imaging results will be compared with histopathology and additionally assessed against literature-reported diagnostic performance and a matched retrospective institutional cohort.

This phase I trial studies the side effects and best dose of modified immune cells (IL13Ralpha2 CAR T cells) after a chemotherapy conditioning regimen for the treatment of patients with stage IIIC or IV melanoma or solid tumors that have spread to other places in the body (metastatic). The study agent is called IL13Ralpha2 CAR T cells. T cells are a special type of white blood cell (immune cells) that have the ability to kill tumor cells. The T cells are obtained from the patient's own blood, grown in a laboratory, and modified by adding the IL13Ralpha2 CAR gene. The IL13Ralpha2 CAR gene is inserted into T cells with a virus called a lentivirus. The lentivirus allows cells to make the IL13Ralpha2 CAR protein. This CAR has been designed to bind to a protein on the surface of tumor cells called IL13Ralpha2. This study is being done to determine the dose at which the gene-modified immune cells are safe, how long the cells stay in the body, and if the cells are able to attack the cancer.

This project aims to assess the expression levels of novel molecular markers identified through screening in clinical samples of malignant pleural effusion, to evaluate the feasibility and clinical utility of these markers as potential diagnostic genes for lung adenocarcinoma.

This research study will help our understanding of whether additional support for Veterans with lung cancer can improve their quality of life.

The present study will explore a novel treatment strategy for unresectable lung adenocarcinoma combining a unique unconventional radiotherapy technique for high dose partial tumor irradiation (PTI) sparing the peritumoral immune microenvironment (PIM) with an immune checkpoint inhibitor (ICI)-based immunotherapy. The present study will focus on patients with larger, unresectable bulky lung tumors who previously failed standard of care therapy, or are unsuitable for conventional radio-chemotherapy due to tumor size and volume, and do not have any further therapeutic option left. This concept implies that a very high, ablative radiation dose (typically 20-25Gy per fraction) is delivered exclusively to the central bulky-tumor segment sparing at the same time surrounding PIM and therefore preserving its function. The present study will explore the potential clinical advantages of the above described innovative treatment concept as a rechallenge treatment: following the disease progression during initiated first-line ICI-therapy, or following discontinuation of ICI-therapy, a same previously used agent (ICI) will be added the PTI to boost its immunologic anti-tumor effects. The treatment response will be measured by comparing the progression-free survival 1 (PFS-1) (ICI-therapy alone) and progression-free survival 2 (PFS-2) (combined rechallange PTI-ICI) rates. The primary endpoint will be ∆PFS rate (PFS-2 vs PFS-1) assessed according to the modified iRECIST criteria. Secondary endpoints will include overall survival, toxicity, and exploration and validation of the anti-cancer immunity. Once treatment is completed, follow up will be performed on a regular basis (at 6 and 12 weeks, and every 3 months later on) by CT, MRT or PET-CT imaging to allow for endpoints assessment, or at any time in case of suspected disease progression. Patients will also be followed clinically with history and physical examinations, vital signs, and laboratory examinations as indicated.

This early phase I trial tests the safety and side effects of dapagliflozin given prior to surgery in patients with stage IA lung adenocarcinoma. Dapagliflozin is approved by the Food and Drug Administration (FDA) for the treatment of diabetes and heart failure. It is an SGLT2 inhibitor. Stage I lung adenocarcinomas express significantly higher levels of the SGLT2 protein than other stages, and research suggests that SGLT2 inhibition improves lung cancer outcomes in patients with diabetes. In this study, dapagliflozin is being used off-label, which means it is being used for a condition that it was not originally approved for by the FDA. The investigational study drug is a neoadjuvant treatment, meaning the drug is given before surgery to try and help make the surgery more effective.

The goal of this Phase II clinical trial (The PHOENIX Study) is to evaluate if the combination of QL1706 (Iparomlimab and Tuvonralimab), bevacizumab, and chemotherapy can treat patients with TKI-refractory, driver-gene positive (e.g., EGFR, ALK, ROS1, RET, KRAS, BRAF, HER2), non-squamous non-small cell lung cancer (NSCLC) who have high PD-L1 expression (TPS ≥50%). The main question\[s\] it aims to answer \[is/are\]: Does the quadruple combination therapy improve the Objective Response Rate (ORR) compared to historical chemotherapy data? What are the secondary efficacy outcomes, including Progression-Free Survival (PFS) and Overall Survival (OS)? If there is a comparison group: There is no concurrent control group (this is an open-label, multi-cohort study). Researchers will compare the treatment outcomes of the participants to historical control data (standard platinum-based chemotherapy) to see if the objective response rate (ORR) improves from a historical baseline of 29% to a target of 55%. Participants will: Receive induction therapy every 3 weeks for 4 cycles, consisting of intravenous infusions of QL1706, bevacizumab, pemetrexed, and platinum chemotherapy (cisplatin or carboplatin). Receive maintenance therapy every 3 weeks with QL1706 and bevacizumab for up to 2 years or until disease progression. Undergo regular tumor assessments (CT or MRI scans) to monitor disease status according to RECIST v1.1 criteria. Provide blood samples for safety monitoring and potential biomarker analysis.

The goal of this observational study is to explore whether changes in peripheral blood effector tumor antigen-specific T cells (ETASTs) can predict treatment outcomes in patients with advanced non-small cell lung cancer (NSCLC) receiving chemoimmunotherapy. The study aims to: * Evaluate the relationship between ΔETAST levels (baseline to cycle 2) and progression-free survival * Compare the predictive performance of ΔETASTs with traditional biomarkers (PD-L1, TMB) * Assess whether ΔETASTs can identify patients more likely to benefit from PD-1 inhibitor plus chemotherapy Participants will: * Provide peripheral blood samples at baseline and after cycle 2 of treatment * Undergo ETAST quantification using the CTT-NanoDT technology with TATAN nanoparticles * Have standard tumor assessments every 2 cycles according to RECIST 1.1 criteria * Be followed for progression-free survival and overall survival up to 24 months

This study aims to compare the one-year survival benefit of the association of cryoablation-pembrolizumab-pemetrexed-carboplatin versus pembrolizumab-pemetrexed-carboplatin in metastatic lung adenocarcinoma patients. This is a multicenter, prospective, open-labeled, 2-arm comparative randomized (1:1) phase III trial. Patients will be randomized with a 1:1 ratio into: * Arm A (experimental arm): cryoablation of one visceral lesion or bone metastasis excluding liver and sclerotic bone metastases combined with pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization. * Arm B (standard arm): pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization. Pembrolizumab and pemetrexed-carboplatin will be prescribed and administered at the dose recommended by market authorization. Cryoablation treatment should be performed within 6 weeks after the first administration of pembrolizumab. No treatment switching permitted.

Double lumen tubes (DLT) have become standard of care for one lung ventilation in thoracic and esophageal surgeries. Selection of accurate size of DLT is important to achieve proper one lung ventilation, prevent trauma to airway, easy intubation, prevention of displacement of DLT and adequate oxygenation intraoperatively. There are no definitive guidelines to select the correct size of DLT. The aim of this study is to observe if there is any difference in the number of intubation attempts, intraoperative oxygenation and postoperative sore throat while using 35 Fr DLT size and other DLT size. The research will be conducted between Ashoj 1st 2082 to Chaitra 30 2082 at Manmohan Cardiothoracic Vascular and Transplant Center(MCVTC). Fifty patients aged more than eighteen years undergoing thoracic surgery requiring One Lung Ventilation(OLV) with left sided DLT will be selected for the study. Participants will be randomly assigned to 35 Fr DLT size group or DLT size group according to the height. Patients in both the groups will be given the samepreoperative care, intraoperative care and postoperative care. Besides patient's demography, diagnosis and operative procedure; number of intubation attempts, modified Cromack-Lehane(CL) grade, size of DLT, intraoperative oxygen saturation SpO₂ and postoperative sore throat on day of surgery and first postoperative day will be recorded. Statistical analysis will be done using t- test for independent variable, confidence interval for outcome of sore throat, significance of difference for number of male and female; rates, risk ratio and odds ratio will be calculated using 2x2 contingency table. P ≤ 0.05 will be considered statistically significant. Our expected outcome is 35 Fr DLT are easier to intubate, does not affect intraoperative oxygenation and decrease the incidence of postoperative sore throat.

Second Life Therapeutics is developing SL-28, an allogeneic, non-genetically modified cell-based therapy for the treatment of advanced solid tumours. The company has recently demonstrated a novel, non-genetic approach to modulate immune cell activity through targeted manipulation of the Universal Receptive System. The purpose of this open label, multi-center clinical trial is to evaluate the anti-tumor activity, safety, and pharmacokinetics, single-agent SL-28 in patients with a diverse array of solid tumors. The study includes an initial Phase 1 dose escalation to determine recommended dose(s) for expansion of SL-28 as a monotherapy and Phase 2 expansion cohorts. The study will enroll patients with advanced solid tumours, including those who failed previous lines of chemo- and immunotherapies.

Lung cancer in never-smokers is increasingly recognized as a disease influenced by genetic susceptibility. Aldehyde-metabolizing enzymes, including the ALDH gene family and ADH1B, play key roles in detoxifying reactive aldehydes that can damage DNA and promote oxidative stress. In this study, we will examine whether ten selected genetic variants, nine single nucleotide polymorphisms (SNPs) across five ALDH family genes and one variant in ADH1B are associated with the risk of lung cancer and its major subtypes. Limited epidemiological evidence is currently available on the association between these aldehyde-metabolizing gene variants and lung cancer. This research aims to clarify their potential contribution to the development of lung cancer, particularly among never-smokers.