Active clinical trials for "Lung Neoplasms"

Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer who progressed on First-Line Osimertinib Therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

This prospective, single-center, randomized, controlled study will evaluate the efficacy and safety of sintilimab or placebo in combination with chemotherapy as second-line treatment for patients with stage IV nonsquamous non-small cell lung cancer with wild-type EGFR after failure with platinum-containing chemotherapy. Treatment may continue as long as participants are experiencing clinical benefit as assessed by the investigator, i.e., in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.

Rationale: Pemetrexed is a multi-targeted folate antagonist, which is primarily indicated for the treatment of advanced non-small cell lung cancer (NSCLC) and mesothelioma. Dosing of cytotoxic agents like pemetrexed requires balancing the dual risk of sub-therapy and toxicity. Administration of pemetrexed to patients with a creatinine clearance <45 ml/min is currently not advised. Pemetrexed is dosed based on body surface area (BSA), while renal function and dose are the sole determinants for systemic exposure. This causes 3 major issues: In patients with renal dysfunction, BSA-based dosing may lead to haematological toxicity Patients have to discontinue treatment due to declining renal function, and are withheld effective treatment Even in patients with adequate renal function (GFR >45 ml/min) treatment may be improved by individualized dosing based on renal function, resulting in less toxicity. Also, BSA-based dosing may lead to ineffective therapy in patients with above average renal function. The investigators aim to address these problems. Objective: The overall main objective is to develop a safe and effective individualized dosing regimen for pemetrexed. Study design:IMPROVE-I is a single arm phase II pharmacokinetic safety study using a Simon two stage design to assess the feasibility of renal function-based dosing of pemetrexed in renal impaired patients. Study population: IMPROVE-I includes 23 patients with NSCLC or mesothelioma with an estimated creatinine clearance <45ml/min that meet all other requirements for pemetrexed treatment. Intervention:Patients will be treated with pemetrexed, with dosing based on renal function. As a safety measure, the first dose will be calculated to 50% exposure. After administration, safety and pharmacokinetics are assessed. If tolerated well, dose escalation to reach 100% exposure is performed, including assessment of safety and pharmacokinetics. Main study endpoints: The fraction (percentage) of patients with attainment of therapeutic exposure. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The investigators consider the extra burden from participating in the planned studies limited. The extra interventions compared to routine care, consist of sampling extra blood. The pharmacokinetic assessments require placement of one additional intravenous catheter. To ensure minimal impact of study participation on daily life, a limited sampling strategy will be used. Patients may benefit from participating in IMPROVE I and -II, as they will be treated with a potentially safe and effective drug that is dosed individually, which prevents toxic exposure

Overall survival (OS) of patients with advanced (stage IIIB/IV) non-small-cell lung cancer (NSCLC) remains short after the first line of treatment with a median OS of 12.2 months in non squamous NSCLC and 9.2 months in squamous NSCLC . In this setting the programmed death 1/ligand 1 (PD-1/-L1) were targeted with nivolumab (IgG4) in advanced squamous and nonsquamous NSCLC leading to an increase of the 1-year OS rate of approximately 10-15% in both histologies. Nivolumab, pembrolizumab and atezolizumab are now considered a standard of care in 2nd line advanced NSCLC and in 1st line for pembrolizumab but but prognosis still remains poor in advanced NSCLC. Overall survival (OS) of patients with advanced (stage III/IV) NSCLC remains limited with a median OS of 12.2 months in non-squamous NSCLC and 9.2 months in squamous NSCLC if anti-PD1 alone. It is of around 16 months if pembrolizumab is combined with chemotherapy. Preclinical data indicates that anti-tumor efficacy is increased when anti-PD-1/-L1 are combined with irradiation (IR). Radiotherapy alone can elicit tumor cell death which can increase tumor antigen in the blood stream, favoring recognition by the immune system and its activation against tumor cells outside of the radiation field (="abscopal effect"). IR may also reverse acquired resistance to PD-1 blockade immunotherapy by limiting T-cell exhaustion. Because of these preclinical and clinical data several studies analysing the combination of IR and anti-PD1 in NSCLC are ongoing. Among them, two studies are testing the administration of IR and nivolumab in stage III NSCLC: the NCT02768558 phase III trial (RTOG), and the NCT02434081 phase II trial (ETOP). Antonia et al [2017] tested the use of anti-PD-L1 after chemoradiotherapy in unresectable stage III NSCLC. Median time to distant metastasis was increased (23.2 months vs. 14.6 months, p<0.001). An increase of OS is consequently expected. However, no study involving concurrent RT and pembrolizumab combined with chemotherapy in advanced NSCLC is ongoing, which is the purpose of the present study, NIRVANA-Lung.

Tumor organoids and TILs (and/or peripheral T cells) cultures will be established from fresh tissure of lung cancer and other solid tumors. Coculture will be utilized to screen tumor-responsive T cells which are further selected for monoclonal expansion and TCR cloning for engineered reconstitution of TCR-T cells. After verification by multiple in vitro and in vivo studies, a large number of TCR-T cells will be introduced back into the patients via vein, artery or fine needle punctured to the tumor, or combinations. In this phase I study, the safety, tolerance and preliminary efficacy of the TCR-T cell immunotherapy on human will firstly be assessed.

Durvalumab is a drug that stimulates the immune system to fight lung cancer. Durvalumab is FDA approved to treat lung cancer. Stereotactic body radiation therapy (SBRT) is a newer radiation treatment that gives fewer, but higher doses of radiation than standard radiation. With SBRT, radiation is focused toward the cancer and away from normal surrounding lung tissue. It is possible that when cancer cells are damaged by SBRT Durvalumab may be more effective in activating the immune system. SBRT is a standard FDA approved treatment for early stage (stage 1) lung cancer and is investigational in patients such as yourself with stage 3 lung cancer. The combination of Durvalumab and SBRT is investigational. This study will investigate the effects, good and bad, of the combination of Durvalumab and SBRT.

This research study is studying a targeted therapy as a possible treatment for Non-Small Cell Lung Cancer (NSCLC) with an EGFR mutation. The names of the study drug involved in this study is: - Osimertinib (Tagrisso)

Phase I study with the hypothesis that Pulsed Low Dose Radiation (PLDR) radiation delivery technique can significantly decrease the rate of severe acute esophagitis in patients receiving concurrent Chemo-radiation therapy (CRT) for non-small cell lung cancer or esophageal cancer while maintaining similar efficacy. For these patients, the rate of severe acute esophagitis during concurrent CRT is high (approximately 20%) when conventional external beam radiation is utilized. Severe acute esophagitis can cause many adverse consequences such as severe discomfort, weight loss, hospitalization, interruption/early termination of treatment, and worse surgical complications for those who receive surgery after CRT. PLDR radiation has the potential to maintain the tumor control rates of conventional radiation while decreasing the toxicity to the surrounding normal tissue 29-35. We have completed accrual to a phase I PLDR radiation study, in which patient received palliative re-irradiation with PLDR technique for their metastatic disease in previous irradiated field. In that phase I study, PLDR demonstrated safety for acute toxicities in the setting of re-irradiation for a total dose of 50 Gy, with analysis of 60 Gy pending. The follow up time for that phase I study is limited as most enrolled patients have short overall survival due to their terminal illness. This proposed phase I study is, to our knowledge, the first clinical study with combination of PLDR radiation and concurrent chemotherapy for definitive treatment.

Patients with stage I non-small cell lung cancer have been historically treated with surgery whenever they are fit for an operation. However, an alternative treatment known as stereotactic radiotherapy now appears to offer an equally effective alternative. Doctors believe both are good treatments and are therefore conducting this study to determine if one may be possibly better than the other.

This is a prospective single arme real-world study clinical study, which aims to investigate the overall benefit and safety of consolidative therapy in advanced NSCLC (stage III/IV) patients , who do not progress after front line systemic therapy (chemotherapy, target therapy or immunological checkpoint inhibitors).