Clinical Research Directory

Ivonescimab Alone And With Carboplatin/Pemetrexed For NSCLC

The goal of this clinical trial is to assess the efficacy of ivonescimab monotherapy in patients with advanced non-small cell lung cancer harboring actionable genomic alterations who have received prior targeted therapies and chemotherapy. This clinical trial also aims to assess the efficacy of ivonescimab plus carboplatin/pemetrexed chemotherapy in patients with advanced non-small cell lung cancer harboring actionable genomic alterations other than epidermal growth factor receptor mutations who have received prior targeted therapies but no chemotherapy. The main questions it aims to answer are: * Will ivonescimab alone or together with carboplatin/pemetrexed chemotherapy shrink tumors in the clinical trial's patients? * Will ivonescimab alone or together with carboplatin/pemetrexed chemotherapy effectively influence if the patients' cancer grows, how long the treatment takes to start working, how long the treatment keeps working after it first starts to help, how long the treatment keeps the cancer from getting worse, and overall survival of patients? * How many patients receiving ivonescimab alone or together with carboplatin/pemetrexed chemotherapy will experience treatment-emergent, treatment-related, immune-related, and especially interesting side effects? Patients receiving ivonescimab alone will receive an intravenous infusion of ivonescimab every 3 weeks for up to 24 months. Patients receiving ivonescimab together with carboplatin/pemetrexed chemotherapy will receive separate intravenous infusions of ivonescimab, pemetrexed, and carboplatin every 3 weeks for 4 cycles (each cycle is 21 days). These patients will continue to receive infusions of ivonescimab and pemetrexed every 3 weeks for up to 24 total months.

The Impact of Exercise on the Tumor Microenvironment in Patients With Lung Cancer

There is increased interest and knowledge about the lung cancer tumor microenvironment (TME). Investigators hypothesize that patients with better baseline physiologic health will have better post-operative outcomes and that strenuous exercise will alter the TME and genetic make-up of the tumor, improving the tumor immune response. Investigators aim to identify the peri-operative and clinical outcomes that differ based on pre-operative VO2max, HRV and resting heart rate following resection of early-stage lung cancer. The physiologic states that are individual and measurable with wearable devices include but are not limited to VO2max, heart rate variability (HRV), and average resting heart rate. Investgators hypothesize that a patient's pre-operative physiologic function with higher VO2max, HRV and lower resting heart rate will be associated with improved peri-operative and post-operative outcomes. Second, investigators will compare alterations in TME based on targeted pre-operative exercise (60-80% of their VO2 max for 75min/week x2 weeks) compared to normal activity adults following resection of early-stage lung cancer. Investigators hypothesize that strenuous exercise in the pre-operative period will impact the TME by increasing levels of cytokines.

Neoadjuvant Nivolumab Plus Ipilimumab in Resectable NSCLC (GALAXY 3)

Neoadjuvant immunotherapy followed by surgery has emerged as the standard treatment for locally advanced and resectable non-small cell lung cancer (NSCLC). However, conventional chemotherapy components may increase treatment-related toxicity, particularly in elderly populations. Additionally, the efficacy of preoperative immunochemotherapy for patients with PD-L1 expression \<1% remains to be improved. Emerging evidence has demonstrated that the combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) provides superior responses in the treatment of advanced NSCLC. However, the safety and efficacy of this strategy in the neoadjuvant setting remain controversial. Therefore, this single-arm clinical trial aims to evaluate the safety and feasibility of neoadjuvant nivolumab plus ipilimumab followed by surgery in treating locally advanced and resectable NSCLC.

Liquid Biopsy Assay of EBUS-TBNA Supernatant Fluid for Diagnosing Lung Cancer

Background and aim: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the gold standard of lung cancer staging, yet up to 15% of procedures produce inadequate samples for definite diagnosis or staging. In such cases, more invasive surgical procedures are usually considered. Fluid collected during EBUS-TBNA is centrifuged to produce a pellet for cell block histopathological examination , while the supernatant is usually discarded. It has been demonstrated that this supernatant can provide material for next generation sequencing (NGS) mutation analysis using liquid biopsy (LB) technics when the procedure yielded positive results (tumor cells were demonstrated in the aspirate). We wish to assess whether LB NGS of the supernatant may provide data regarding lymph nodes involvement in non-small cell lung cancer (NSCLC) in cases with a negative EBUS-TBNA evaluation (no tumor cell identified in the aspirate). Methods: A prospective feasibility study which will recruit participants with high suspicion for thoracic lymph nodes involvement in NSCLC who will be subjected to EBUS-TBNA. The final study group will comprise of 10 subjects with a negative EBUS-TBNA evaluation (no tumor cell detected) who will require surgical resection of the thoracic lymph nodes. EBUS-TBNA collected fluid will be centrifuged and separated. Cellular pellets will undergo cytological and histopathological evaluation, including tissue NGS, as usual. Cell-free DNA will be extracted from the supernatant and will undergo separate LB NGS targeted to genes frequently mutated in NSCLC. We will assess the concordance between the positivity of supernatant NGS and surgical lymph nodes staging, and the concordance between supernatant NGS and blood NGS. Expected results: We expect high concordance between surgical lymph nodes staging and supernatant NGS, that is, genetic mutations would be identified by the supernatant NGS in subjects with lymph nodes involvement by tumor, and not in those without it. Importance to Medicine: NSCLC is the leading cause of cancer mortality. Improving the effectiveness of EBUS-TBNA may reduce the need for additional invasive procedures, increase accuracy and reduce turnaround time of specimens.

Utilizing Long-read Sequencing to Investigate the EGFR Landscape of EGFR Positive Lung Cancer Patients

EGFR gene mutations are some of the most commonly occurring mutations in non-small cell lung cancer. Investigators have developed a DNA instability model that estimates a risk score to assess the likelihood of an individual acquiring a cancer-linked mutation. The aim of this study is to collect blood from both those diagnosed with EGFR positive lung cancer and healthy individuals, evaluate their gene sequence surrounding the EGFR landscape and use the cancer positive and healthy sequences to validate the risk assessment model, which may one day be used to provide insight on susceptibility of getting EGFR positive lung cancer or potentially other cancer types.

Standard Care With or Without Early Palliative Care Provided by Palliative Care Specialist in Advanced Non-small Cell Lung Cancer Patients

Early palliative care has been shown to improve the survival of advanced lung cancer patients. However, most of the clinical studies were performed in the era when systemic treatment options for this disease were limited. Currently, many effective treatment options are available, including targeted therapy and immunotherapy. These novel agents improve the treatment outcomes while having less toxicity compared to conventional chemotherapy. Moreover, medical oncologists are now trained to provide palliative care for patients. This study was designed to demonstrate whether early palliative care provided by the palliative care specialist still improves the quality of life or survival of advanced lung cancer patients compared to standard care provided by the medical oncologist.

Transbroncheal Novel PDT Peripheral Lung Tumor Ablation With 5-ALA

Photodynamic therapy (PDT) involves the use of special light-sensitive drugs that are selectively absorbed by cancer cells. When exposed to a specific wavelength of light, these drugs are activated within the tumor cells, triggering a free radical reaction that destroys the cancer cells. Currently, PDT is used in the treatment of early-stage lung cancer in the central airways or for advanced tumors causing airway obstruction. With advancements in medical technology, electromagnetic navigation bronchoscopy (EMB) can now be employed in a hybrid operating room (Hybrid OR) under radiological guidance to direct photodynamic therapy fibers to the tumor site for light therapy. Our research team previously proposed a novel light transmission method, using Sodium Porfimer as the photosensitizer. In the Hybrid OR, electromagnetic navigation bronchoscopy was utilized to infuse Lipiodol into the bronchial tree, enhancing the illumination range through the optical fiber effect. Energy of 630 nm at 200 J/cm (400 mW/500 seconds) delivered through a 3 cm cylindrical laser fiber was deemed safe, with no significant acute complications observed. However, due to the low light dosage, the therapeutic outcome was suboptimal, although one case demonstrated tumor necrosis with no apparent damage to the surrounding lung tissue. A second-phase pilot clinical trial aimed at improving light energy and treatment coverage through a multi-session, multi-angle light exposure model is also proved this method is feasible and safe. In addition to Sodium Porfimer, other photosensitizers are approved for clinical use in photodynamic diagnosis and therapy. For example, 5-Aminolevulinic Acid (5-ALA) has been approved for the treatment of brain cancer surgery. Similar to Sodium Porfimer, 5-ALA is a precursor of heme, and in certain cells (such as cancer cells and reticuloendothelial tissues) where there is a deficiency of the enzyme ferrochelatase, administering large amounts of 5-ALA or Sodium Porfimer leads to the accumulation of Protoporphyrin IX (PpIX). PpIX is a photosensitizer, and when exposed to a specific wavelength of light, it generates oxygen free radicals that destroy cancer cells, thereby producing the therapeutic effect of PDT. We propose this clinical trial to explore the use of 5-ALA as a substitute for Sodium Porfimer in the novel PDT treatment of peripheral lung tumors. Compared to Sodium Porfimer, 5-ALA has the same therapeutic mechanism but a shorter half-life. It can be taken orally 2-4 hours before treatment, requires only one day of light protection post-procedure, and is more cost-effective. 5-ALA (Gliolan) has also been approved by the FDA for photodynamic diagnosis and treatment of brain cancer, and clinical trials in other cancers have demonstrated its safety and feasibility. This phase 0 pilot clinical study plans to recruit six patients with peripheral malignant lung tumors (tumor diameter ≤ 30 mm). 5-ALA (Gliolan) will be used as the photosensitizer, and in the hybrid operating room, electromagnetic navigation bronchoscopy will guide a catheter to the tumor site. Lipiodol (iodized poppy seed oil) will be infused to coat the tumor, enhancing the light exposure range. The first three subjects will undergo a single-session light exposure to assess the feasibility and safety of the procedure. The remaining three subjects will receive multi-session, multi-angle light exposure to further verify the safety and effectiveness of the treatment. The findings from these subjects will serve as a reference for light energy parameters for future phase I clinical trials.