View clinical trials related to Adenocarcinoma.
Filter by:This study will assess if endoscopic ultrasound radiofrequency application in patients with inoperable pancreatic cancer and chemotherapy confers survival benefit when compared to patients receiving best medical care and chemotherapy .
This research study is being down to find what, effects, good and/or bad, adding Pembrolizumab to standard chemotherapy mFOLFOX before and after surgery have on the patient and the patient's cancer.
Lung cancer is the leading cause of cancer mortality in France and worldwide. 60% of patients present themselves with a disease diagnosis immediately metastatic non curable. Adenocarcinomas account for 50% of incident tumors. Treatment is based on the platinum-based chemotherapy with or without maintenance therapy. When there is to exhaust this first line, a second line treatment is offered to the patient. Three drugs are allowed in this situation: docetaxel, erlotinib (inhibitor of the tyrosine kinase activity of the receptor for epidermal growth factor - TKI-EGFR) and pemetrexed (which in fact has become virtually standard in first online and in combination with platinum in all patients with non-squamous cancer, so that his place is in second line reduced facto). There is no recommendation for treatment in third line situation where only erlotinib is allowed. Most recently, the nivolumab, anti-PD1 monoclonal antibody (which aims to enable immunutaire system) saw its demonstrated effectiveness in the second line and beyond in the two Phase 3 trials where it was compared with docetaxel for the treatment of squamous cell carcinoma and non-squamous. The very recent availability in France of the drug under an ATU fact that it will most likely become a standard second line, which will tend to place the third line docetaxel. Therefore, erlotinib will be in 4th line situation. However, in the absence of an EGFR mutation (which is only seen in more than 10% of Caucasian patients) use of the drug does not seem appropriate or even harmful. A selection of patients likely to benefit from the prescription of EGFR TKI-is essential. Neurotensin (NTS) is a polypeptide of 13 amino acids present and active in the central nervous system and the periphery. At the peripheral level, neurotensin is secreted postprandial by endocrine cells in the intestinal mucosa and is involved in the motor functions of the gastrointestinal tract. The effects of neurotensin pass through the activation of three subtypes of receptors which, mainly, NTSR1 and NTSR2 which are receptors coupled to G proteins in the extra-digestive normal tissues, including lung, torque NTS / NTSR1 n is not expressed physiologically. Rather, this complex is likely to recur in tumor tissues. The mechanism of this effect is derogatory activation torque NTS / NTSR1 of matrix metalloproteinases which causes the release by the cell membrane ligands "EGF-like" and thus, activation of HER receptor (EGFR or HER1, HER2 and HER3). Indeed, in experimental tumors created by subcutaneous injection in athymic mouse cell lines adenocarcinomas NTS + / NTSR1 + (non-mutated EGFR), treatment with erlotinib - which blocks EGFR pathway - causes a significant decrease of tumor growth. Expression of the neurotensin receptor in cancer cells metastatic primary bronchial adenocarcinoma is not known. Therefore, its pejorative prognostic value is not confirmed in the metastatic setting.
Research Hypothesis: The combination of ionizing radiation and immunotherapy (durvalumab) is well tolerated and stimulates a clinically significant pancreas-cancer specific immune response. The primary objective will be to evaluate whether the combination of RT and durvalumab can improve median PFS compared to chemotherapy historical control data in metastatic pancreas cancer patients who have progressed through first-line chemotherapy. The primary intent of RT in this study is to augment a pancreatic cancer-specific immune response when given with durvalumab.
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.
This is a prospective, multicenter, randomized, placebo-controlled, triple-blind phase II trial. The randomization will be a 1:1 randomization (experimental arm:control arm). This study will enroll patients with histologically confirmed esophagogastric adenocarcinoma with metastatic disease. Patients will have had no previous chemotherapy for metastatic esophagogastric cancer. Patients will receive nintedanib or placebo in combination with mFOLFOX6 (5-Fluorouracil 400 mg/m2 bolus on day 1, 5-Fluorouracil 2400 mg/m2 continuous infusion over 46 hours starting on day 1, Leucovorin 400 mg/m2 on day 1, Oxaliplatin 85 mg/m2 on day 1) via IV infusions every 2 weeks (14 days). Dose modification of nintedanib or placebo and mFOLFOX6 is allowed. Patients may continue to receive protocol therapy as long as they have not experienced any adverse events requiring permanent discontinuation of study medication and have not demonstrated disease progression. The primary objective is to test the hypothesis that progression free survival (PFS) is prolonged in HER2-negative patients with untreated metastatic esophagogastric adenocarcinoma when treated with nintedanib plus modified FOLFOX6 (mFOLFOX6) as compared to placebo plus mFOLFOX6. The analyses will be performed when 124 events for PFS will have been observed in the pooled arms.
This single-center, prospective proof-of-concept study is designed to evaluate the surgical outcomes and clinicopathologic results of neoadjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in conjunction with perioperative systemic chemotherapy (SCT; neoadjuvant and adjuvant) and pancreaticoduodenectomy (PD) in a small cohort of patients having T1-T3 resectable pancreatic ductal adenocarcinoma (PDAC) with one or more high-risk clinical features. The investigators hypothesize that HIPEC administered in this clinical course will reduce postoperative peritoneal disease recurrence. The investigators also expect that local recurrence of disease will be reduced. The primary aim of this study is to compare 2-year peritoneal disease-free survival between patients receiving the experimental therapy (neoadjuvant HIPEC + SCT + PD) with historical controls receiving standard therapy (SCT + PD). Secondary aims are to determine the clinical feasibility and outcomes of neoadjuvant HIPEC for resectable PDAC using patient demographics and disease characteristic data.
This phase I/II trial studies how well birinapant and carboplatin work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back. Drugs used in chemotherapy, such as birinapant and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
The goal is to improve surgery by preventing tumor cells from being left behind at the time of surgery. This includes finding residual tumor cells in the wound after surgery.
This phase I trial studies the side effects and best dose of talazoparib and heat shock protein (HSP)90 inhibitor AT13387 when given together in treating patients with solid tumors that have spread to other places in the body (metastatic) or ovarian, fallopian tube, primary peritoneal, or hormone negative breast cancer that have come back after a period of improvement (recurrent). Talazoparib and HSp90 inhibitor AT13387 may stop the growth of tumor cells by blocking some enzymes that are need for cell growth. HSp90 inhibitor AT1338 may also help talazoparib work better by making tumor cells more sensitive to the drug.