NCT05172739Phase 4Recruiting
University of Crete · University of Crete, Heraklion, Crete
Lobectomy is a major, high-risk surgical procedure that in addition to one-lung ventilation (OLV) exerts a potent surgical stress response. An overwhelming immune cell recruitment may lead to excessive tissue damage, peripheral organ injury and immunoparesis. The effect of anesthesia on the immune system is modest, compared to the effects induced by major surgery. However, to an immunocompromised patient, due to cancer and/or other comorbidities, the immunosuppressive effects of anesthesia may increase the incidence of post-operative infections, morbidity, and mortality. Exogenous opioids have been correlated with immunosuppression, opioid-induced hyperalgesia, and respiratory depression, with deleterious outcomes. An Opioid-Free Anaesthesia-Analgesia (OFA-A) strategy is based on the administration of a variety of anaesthetic/analgesic and other pharmacological agents with different mechanisms of action, including immunomodulating and anti-inflammatory effects. Our basic hypothesis is that the implementation of a perioperative multimodal OFA-A strategy, will lead to an attenuated surgical stress response and attenuated immunosuppression, compared to a conventional Opioid-Based Anaesthesia-Analgesia (OBA-A) strategy. The aforementioned effects, are presumed to be associated with equal or improved analgesia and decreased incidence of postoperative infections compared to a perioperative OBA-A technique.
Eligibility: 18 Years to 80 Years · All · * patients undergoing elective VATS lobectomy
* early stage NSCLC (up to T3N1M0)
NCT05244239Phase 1Recruiting
Emory University · Emory University Hospital Midtown, Atlanta, Georgia
This phase I trial aims to determine if it is safe to use palliative radiotherapy and lurbinectedin at the same time to treat small cell lung cancer that has spread outside of the chest and that has grown after being treated with chemotherapy (extensive stage). Lurbinectedin kills tumor cells by blocks a process called transcription that small cell lung cancer relies on to survive. It also damages the deoxyribonucleic acid (DNA) of tumor cells, which is similar to the way radiation kills tumor cells. Palliative radiotherapy is a routine medical treatment for patients who have lung cancer that has spread to other parts of the body (metastatic), and is used to relieve symptoms caused by cancer or to patients from developing symptoms. This trial may help doctors understand if treating patients with lurbinectedin and palliative radiotherapy at the same time would make them both work better than either one alone or if they could cause more side effects for patients when given together.
Eligibility: 18 Years to · All · * Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 3
* Patients with pathologically confirmed ES-SCLC who are receiving lurbinectedin or are candidates for lurbinectedin therapy after progression on first-line systemic therapy (either chemotherapy \[platinum etoposide\] or chemoimmunotherapy) at the discretion of the treating medical oncologist.
* Metastatic bone or visceral/lung metastatic disease as assessed computed tomography (CT), magnetic resonance imaging (MRI), bone scan or positron emission tomography (PET)/CT within 90 days prior to RT on this study.
* Patients with treated brain metastases are eligible but must require \< 10 mg of dexamethasone daily or its glucocorticoid equivalent. Brain metastases will not be treated in the context of this protocol.
* Absolute neutrophil count (ANC) \>= 1,500/cells/mm\^3
* Platelets \>= 100,000/cells/mm\^3
* Hemoglobin \> 7.0 g/dL
* Total Bilirubin ≤ 1.5 ULN
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3.0 x ULN (=\< 5.0x ULN for liver involvement)
* Alkaline phosphatase =\< 2.5x ULN (=\< 5.0x with documented liver or bone metastases)
* Based on its mechanism of action, lurbinectedin could cause harm when administered to a pregnant woman. Taken together with the known teratogenicity of RT, female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting protocol therapy. A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months.
* FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 6 months after the final dose of lurbinectedin. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of lurbinectedin administration. FCBP who are currently breastfeeding must discontinue during and up to 2 weeks after the final dose of lurbinectedin.
* Completion of all previous cancer-directed therapies (excluding lurbinectedin) for the treatment of cancer \>= 3 weeks before the start of study therapy.
* Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions.
* Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.
NCT06830694Phase 2Recruiting
Sehhoon Park · Samsung Medical Center, Seoul, Gangnam-gu
The primary treatment option for non-small cell lung cancer (NSCLC) adenocarcinoma (ADC) with activating epidermal growth factor receptor (EGFR) mutation is EGFR tyrosine kinase inhibitor (TKI). After a certain period of treatment with EGFR TKI, acquired resistance emerges most frequently with a secondary mutation, p.T790M (36-50%), followed by MET amplification (10-19%). Interestingly, up to 3-5% of patients experience histological transformation into small cell lung cancer (SCLC).
As an underlying mechanism, ADC with a predisposed clonally inactivated Rb and p53 mutation and APOBEC mutation signature is known to be associated with SCLC transformation. The transformed SCLC harbors similar morphological and immunohistochemical (IHC) characteristics as those observed in de novo SCLC, including high expression of chromogranin and synaptophysin. However, little is known about the clinical outcomes of transformed SCLC, with limited studies arguing that their outcomes are similar to those of de novo SCLC, where the median overall survival is approximately 9 to 10 months after the transformation.
As the first line treatment of SCLC, atezolizumab or durvalumab with four cycles of conventional chemotherapy followed by maintenance therapy demonstrated prolonged overall survival (OS) and placed as the standard treatment option. However, median progression-free survival (PFS) of both study was only 5.2 months and 5.1 months, despite the objective response rate showing 60.2% and 79%. This finding suggest further development of maintenance treatment strategy to prolonged longer duration of response to the treatment.
In addition to the conventional treatment, Tarlatamab (AMG757), bispecific t-cell engager (BiTE), designed to engage DLL3 on SCLC and CD3 on T-cell has been tested in SCLC. DLL3 is expressed in more than 80% of patients with SCLC, regardless of disease stage and researched for the potential target protein for the antibody based treatment in SCLC. By targeting DLL3 using Tarlatamab, engagement of tumor antigen and CD3 lead to cytotoxic synapse formation, triggering the release of proinflammatory cytokines, perforin, and granzymes from activated T-cells, potentially resulting apoptosis. The first clinical outcome of Tarlatamab was reported from the DeLLphi-300 study, phase 1 dose exploration study, showing confirmed partial response in 23% of the heavily treated SCLC and 37% of the patients showed decrease in tumor burden. Median duration of response was 13.0 months (95% confidential interval CI: 6.2 - 14.9 months), median PFS of 3.7 months and median OS was 13.2 months. In the treatment naïve SCLC, DeLLphi-303 study, phase 1b study combining tarlatamab + PD-L1 inhibitor + carboplatin and etoposide, is ongoing to evaluate the clinical efficacy in the front line setting which include only histologically confirmed extensive disease SCLC population (NCT05361395).
Based on previous clinical and pre-clinical outcomes, showing similar disease characteristics between transformed SCLC from the adenocarcinoma who treated with EGFR TKI with de novo SCLC, this study is designed to evaluate the clinical efficacy of tarlatamab with currently standard treatment in transformed SCLC.
Eligibility: 19 Years to · All · 1. Histologically confirmed SCLC and no prior systemic treatment for SCLC
2. Patient initially diagnosed with activating EGFR mutation (L858R, Del 19) and treated with any kind of EGFR TKI.
3. Confirmed SCLC transformation right after EGFR TKI treatment failure.
4. Age ≥19 years
5. ECOG performance status of 0 to 1
6. Had at least one measurable lesion.
7. Adequate organ function
* Absolute neutrophil count ≥ 1.5 x 109/L
* Platelet count ≥ 100 x 109/L
* Hemoglobin ≥ 9 g/dL
* Estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation \> 30 mL/min/1.73 m2
* Aspartate aminotransferase and alanine aminotransferase ≤ 3 x upper limit of normal (ULN) (or ≤ 5 x ULN for subjects with liver involvement)
* Total bilirubin ≤ 1.5 x ULN (or ≤ 2 x ULN for subjects with liver metastases)
* Prothrombin time (PT)/international normalized ratio and partial thromboplastin time or activated partial thromboplastin time ≤ 1.5 x institutional ULN Note: Subjects on stable anticoagulation therapy are allowed.
8. Pulmonary function: No clinically significant pleural effusion at the timepoint of screening. Pleural effusion with no significant symptom is allowed for enrollment.
9. Cardiac function: Cardiac ejection fraction ≥ 50%
10. Female subjects must either be of non-reproductive potential
11. Female subject with reproductive potential can be enrolled with agreement to following guidance.
* subject uses contraception during treatment and through 60 days after receiving last dose of tarlatamab or for 6 months after last dose of carboplatin and/or etoposide and 5 months after last dose of atezolizumab.
12. Subject is willing and able to comply with the protocol
13. Signed written informed consent
NCT03199651NARecruiting
Ohio State University Comprehensive Cancer Center · Ohio State University Comprehensive Cancer Center, Columbus, Ohio
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.
Eligibility: 18 Years to · All · * AIM 1-3
* Pathologically confirmed stage IV NSCLC (with any Eastern Cooperative Oncology Group \[ECOG\] performance status, and any NSCLC - adenocarcinoma, squamous cell, etc.) with available imaging OR patients who do not yet have their staging completed, but in the judgment of the physician are likely to be stage IV;
* Patients may be enrolled if the recruiter cannot reach the patient by the first office visit, preferably prior to starting therapy and no later than one month after starting therapy; (NCCN guidelines allow for a switch to targeted therapy from chemotherapy if testing comes back positive after starting chemotherapy)
* English speaking; and
* Willing to provide access to medical records, insurance and billing data, biospecimens and respond to questionnaires, typically by phone, but possibly to include online or in-person surveys
* AIM 3 ONLY
* Patients must be current smokers who smoke at least one cigarette most days per week, or recent quitters who smoked at least one cigarette most days per week (\< 3 months); and
* Household members must be current smokers, defined as smoking at least one cigarette most days per week
* Hearing and vision impairments that would prevent ability to complete consent, interviews, or sample collection
NCT06529822Phase 1Recruiting
Washington University School of Medicine · AdventHealth, Orlando, Florida
This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine strategy in patients with solid tumors and molecular residual disease. The hypothesis of the trial is that synthetic long peptide personalized cancer vaccines will be safe and capable of generating measurable neoantigen-specific T-cell responses enabling ctDNA clearance. The personalized cancer vaccines are composed of synthetic long peptides corresponding to prioritized cancer neoantigens and will be co-administered with poly-ICLC.
Eligibility: 18 Years to · All · Inclusion Criteria Cohort #1:
* Age ≥ 18 years.
* ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
* Histologically confirmed muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (renal pelvis and/or ureter).
* Patients with carcinomas showing mixed histologies are required to have a dominant transitional cell pattern.
* Complete surgical resection of MIBC (R0) or upper tract urothelial carcinoma (renal pelvis and/or ureter). Tumor, nodes, metastases (TNM) classification (based on the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th ed.) at pathological examination of surgical resection specimen as follows: ypT0N0M0, pT2-4N0M0, or pT0-4aN+M0.
* Patient must have fully recovered from surgical resection in the opinion of the treating MD.
* ctDNA positive result as identified by Signatera.
* Radiologic confirmation (by conventional imaging) of absence of residual disease and absence of metastasis.
* Adequate bone marrow and organ function as defined below:
* WBC ≥ 1.5 K/cumm
* Absolute neutrophil count ≥ 1.0 K/cumm
* Platelets ≥ 50 K/cumm
* Hemoglobin ≥ 8.0 g/dL
* Total bilirubin ≤ 1.5 x IULN
* AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
* Creatinine clearance \> 30 mL/min by Cockcroft-Gault
* The effects of synthetic long peptide personalized cancer vaccines and Hiltonol on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 5 months after completion of study interventions. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
* No concurrent investigational therapies outside of this protocol are allowed.
* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria Cohort #1:
* Receiving any other investigational agents, or planning to receive other investigational agents as part of neoadjuvant therapy. Patients who have received perioperative neoadjuvant chemotherapy and immunotherapy, including enfortumab vedotin plus pembrolizumab (EV+P), are allowed.
* Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
* A psychiatric illness or social situations that would limit compliance with study requirements as determined by the investigator from the medical history, physical exam, and/or medical record.
* Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. In the case of asthma or chronic obstructive pulmonary disease taking inhaled corticosteroids that does not require daily systemic corticosteroids is acceptable. Additionally, local acting steroids (topical, inhaled, or intraarticular) will be allowed. Patients on intermittent or short course steroids will be allow if the dose does not exceed 4 mg of dexamethasone (or equivalent) per day for \> 7 consecutive days. Premedication for chemotherapy does not apply to this criterion and may be administered as per SOC practice. Any patients receiving steroids should be discussed with the PI to determine if eligible.
* Known HIV-positive status.
* History of positive test for Hep
NCT06739031NARecruiting
Energenx Medical LTD. · Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine,, Shanghai
The goal of this clinical trial is to verify the efficacy and safety of pulsed electric field (PEF) treatment of early-stage unreseectable non-small cell lung cancer(NSCLC) patients.
The main questions it aims to answer are:
* Safety of PEF treatment of early-stage unreseectable NSCLC patients.
* Locoregional control of ablated lesions.
* Survival and quality of life assessment of early-stage unreseectable NSCLC patients.
Eligibility: 18 Years to · All · Inclusion criteria (all requirements must be met at the same time):
1\. Age ≥ 18 years old; 2. Pathological diagnosis of non-small cell lung cancer, with the maximum diameter of the tumor ≤ 3 cm and the number ≤ 3; 3. ECOG score ≤ 2 points; 5. According to the evaluation of the researcher, it is technically feasible to perform ablation treatment on the lesion; 6. The subject agrees to receive ablation treatment and signs the informed consent form.
Exclusion criteria (if any of the above conditions are met, the patient will be excluded):
1. The subject cannot tolerate or refuses general anesthesia;
2. Has a history of severe allergic reactions;
3. Has contraindications to bronchoscopy or refuses bronchoscopy;
5\. Has active implants in the chest cavity or metal implants in the lung to be treated; 6. Uncorrectable coagulation abnormalities (INR\>1.5 or APTT\>1.5 ULN), with bleeding tendency; anticoagulant therapy and/or antiplatelet drugs are discontinued before ablation for no longer than the prescribed safety period; platelets \<50×10\^9/L; 7. Severe liver and kidney dysfunction, assessed by the researchers as unsuitable for inclusion; 8. Accompanied by infectious diseases that cannot be effectively controlled; 9. Subjects with other severe lung diseases (including severe interstitial pneumonia, pulmonary fibrosis, pulmonary fibrosis combined with emphysema, atelectasis, etc.), assessed by the researchers as unsuitable for inclusion 10. Acute cardiovascular and cerebrovascular accidents such as acute cerebral infarction, acute coronary syndrome, etc. within 3 months; 11. Subjects with severe cardiac dysfunction; history of severe arrhythmias in the past 2 years, including rapid atrial arrhythmias, any rapid ventricular arrhythmias; history of II degree type II or III degree atrioventricular block; and sinus bradycardia with a heart rate of less than 45 beats per minute, etc.; 12. Subjects have participated in or are participating in other clinical trials within three months; 13. Pregnant, lactating women, or women who plan to become pregnant during the study; 14. Subjects determined by the researchers to have other conditions that are unsuitable for inclusion.
