Active clinical trials for "Small Cell Lung Carcinoma"

RATIONALE: Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as etoposide and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panobinostat together with etoposide and cisplatin may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with etoposide and cisplatin as first-line therapy in treating patients with extensive-stage small cell lung cancer.

The majority of lung cancer patients have a tumor-derived genetic alteration in circulating plasma DNA that could be exploited as a diagnostic tool. The aim of this study is to evaluate if plasma DNA can be used as a valuable non invasive test to monitor disease progression without assessing the tumor.

This phase I/II trial is studying how well fludeoxyglucose F 18 PET scan, CT scan, and ferumoxtran-10 MRI scan finds lymph node metastasis before undergoing chemotherapy and radiation therapy in patients with locally advanced cervical cancer or high-risk endometrial cancer. Diagnostic procedures, such as a fludeoxyglucose F 18 positron emission tomography (PET) scan, computed tomography (CT) scan, and ferumoxtran-10 magnetic resonance imaging (MRI) scan, may help find lymph node metastasis in patients with cervical cancer or endometrial cancer.

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective for treating extensive-stage small cell lung cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of combining topotecan and paclitaxel with that of combining etoposide and cisplatin in treating patients who have extensive-stage small cell lung cancer.

This phase II trial studies how well pembrolizumab and epacadostat work in combination treating patients with extensive stage small cell lung cancer. Monoclonal antibodies, such as pembrolizumab, may assist the immune system in recognizing cancer cells leading to elimination of those cells. Epacadostat may prevent down-regulation of T-cells, which means it can boost the immune system. Giving pembrolizumab and epacadostat together may work better than either drug alone in treating extensive stage small cell lung cancer.

This study is a single-arm, open-label, multicenter phase 1/2 trial designed to establish the recommended phase 2 dose (RP2D) of daily oral venetoclax when given in combination with irinotecan in patients with relapsed or refractory small cell lung cancer (SCLC).

REFIT-MSS is a non-randomized, multicenter, open-label, multi-cohort, 2-stage, phase II trial to evaluate the efficacy and safety of regorafenib in combination with tislelizumab (referred as Rego-Tisle) in adult patients with select advance, previously treated, Mismatch Repair-Proficient/Microsatellite (pMMR/MSS) stable solid cancers. The multi-cohort design will allow for the examination of 8 separate cohorts of different cancers to determine whether further examination may be warranted in the individual indications.

Both metastatic squamous non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (SCLC) are incurable with current therapies, but due to mutations induced by cigarette smoke, typically express a large number of altered proteins that can be recognized as foreign by the immune system. This antigenicity is thought to explain the efficacy of pembrolizumab as either a first or second line treatment in this disease. For patients who receive chemotherapy plus immunotherapy as a first line therapy, there is sound rationale for combination treatment with immunotherapy and a therapeutic antitumor vaccine as a maintenance strategy. Regardless of PD-L1 expression in the tumor, monoclonal antibodies that block PD-1/PD-L1 interactions are effective second line therapies after chemotherapy in both NSCLC and SCLC. In addition, by targeting the immune system against tumor specific antigens using a peptide vaccine, the efficacy of pembrolizumab alone is expected to be enhanced, with an improved response rate and prolonged overall survival with no additional toxicity. This pilot study will provide a preliminary test of the feasibility of generating a personalized, tumor neoantigen-specific therapeutic vaccine and the safety of combining it with checkpoint blockade immunotherapy.

Lung cancer is the leading cause of cancer deaths in France, Europe and the world. 50% of lung cancers are of the adenocarcinoma subtype. 60% of patients present with a metastatic disease (stage IV) at the time of diagnosis. Approximately 10% of patients present with a mutation of the epidermal growth factor receptor (EGFR) requiring an EGFR tyrosine kinase inhibitor (EGFR-TKI), namely erlotinib, gefitinib or afatinib. For the majority of chemotherapy-naïve patients without addictive mutation, platinum-based chemotherapy, frequently the platinum - pemetrexed doublet, provides disease control rate of up to 70% and improves survival from approximately 4.5 with best supportive care alone to 15 months. However, patients with non-small cell lung cancer (NSCLC) usually relapse within 4 to 6 months and benefit from a second-line chemotherapy. Authorized drugs in this setting are pemetrexed, docetaxel and erlotinib. The prescription of erlotinib for unselected patients whose tumor does not harbor an EGFR mutation is questionable . In the second line setting, docetaxel provides less than 10% of partial responses and progression-free survival of 10 to 12 weeks. There are no standard options following failure of two previous lines of standard chemotherapy. In view of these modest results, new agents and therapeutic strategies are greatly needed for this patient population. Neurotensin (NTS) is a 13 amino acids peptide, present and biologically active in the central nervous system and in periphery. At the peripheral level, NTS is released by the endocrine cells of the intestinal mucosa after meals and acts as an endocrine hormone involved in the postprandial regulation of the motor functions of the gastrointestinal tract. The effects of NTS are mediated by three subtypes of receptor: NTSR1 and NTSR2 exhibit high and low affinity for NTS, respectively, and belong to the family of G protein receptors; NTSR3 is a single transmembrane domain receptor. Exogenous activation of NTSR1 leads to cell proliferation, survival, mobility and invasion in cancer cells from diverse origin. These effects are the result from the activation of kinases and effectors, such as PKC, MAPK, FAK, RHO-GTPase, RAS and Src. The PKC activation may induce MAPK by direct stimulation of Raf-1, or by transactivation of the EGFR. The activation of MAPK via NTSR1 is mainly associated with uncontrolled cell growth. Both NTS and NTSR1 are expressed in 40% of lung tumors, whereas they are never expressed in the normal tissue. NTSR1 high expression is a negative prognostic factor in stage I to III operated lung adenocarcinomas. Sustained stimulation of NTSR1 results in the activation of MMP1, the release of EGF "like" ligands such as HB-EGF as well as neuregulin 1 NGR1 (a specific ligand for HER3) followed by EGFR, HER2 and HER3 overexpression and activation. Accordingly, xenografted tumors expressing NTS and NTSR1 show a positive response to erlotinib, whereas tumors void of NTSR1 expression have no detectable response. Afatinib (BIBW2992) is a small molecule, selective and irreversible erbB family blocker. In preclinical models it effectively inhibits EGFR, HER2 and HER4 phosphorylation resulting in tumour growth inhibition and regression of established subcutaneous tumours derived from four human cell-lines known to co-express ErbB receptors. Our claim is that patients harbouring the NTS/NTSR complex, without EGFR mutation, will respond to afatinib due to the sustained activation of EGFR/HER2 under neurotensin activation. Presently, only EGFR mutated tumors are eligible to receive EGFR TKI representing 10% of all lung cancer patients. The aim of this study is to evaluate the efficacy of afatinib, an EGFR TKI, on lung adenocarcinomas, EGFR wild-type, bearing the NTS/NTSR1 complex with a high level of expression. This subpopulation of patients represents approximately 20% of lung adenocarcinomas.

The hypothesis of this study is that the addition of NovoTTF-100A System treatment to salvage chemotherapy will significantly increase time to treatment failure in the brain of small cell lung cancer patients.