Archives: Clinical Trials

A study to evaluate AGS-1C4D4 administered in combination with Gemcitabine chemotherapy in subjects with Metastatic Pancreatic Cancer.

This phase I pilot trial studies the side effects of cluster of differentiation 8 (CD8)+ T cells in treating patients with gastrointestinal tumors that have spread to other places in the body. Tumor cells and blood are used to help create an adoptive T cell therapy, such as CD8+ T cell therapy, that is individually designed for a patient and may help doctors learn more about genetic changes in the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CD8+ T cell therapy and pembrolizumab may work better in treating patients with gastrointestinal tumors.

This phase II trial studies how well giving selumetinib and erlotinib hydrochloride together works in treating patients with locally advanced or metastatic pancreatic cancer that is refractory to chemotherapy. Selumetinib and erlotinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

The incidence rate of pancreatic neuroendocrine neoplasms (pNENs) is increasing year by year. According to the statistical results of the SEER (Surveillance, Epidemiology, and End Results) database, the incidence rate of pNENs increased from 0.27/100000 to 1/100000 from 2000 to 2016, with a median overall survival time of 68 months. The 5-year overall survival rates of localized, locally advanced, and metastatic pNENs were 83%, 67%, and 28%, respectively. pNENs are gradually gaining attention and importance from the medical community. The existing therapeutic drugs for neuroendocrine tumors include somatostatin analogues, recombinant human interferon injections, chemotherapy drugs, and molecular targeted drugs.

Although these drugs can prolong patients' PFS to some extent, there is a common problem of low objective response rates. In recent years, sunitinib and everolimus have been approved for targeted therapy in patients with pancreatic neuroendocrine neoplasms , but their clinical efficacy is still limited. The study by Panzuto et al. showed that the median PFS for first-line treatment of advanced well differentiated pancreatic neuroendocrine neoplasms was 13.9 months, with an ORR of 14.9%. After imaging progression of the disease, the median PFS after second-line treatment was 15 months, and the ORR of only 5.5%. There is currently no effective treatment for patients with disease progression or drug resistance after undergoing existing treatment ways.

Therefore, there is a huge clinical demand for the treatment of pNEN patients worldwide, and effective drugs are urgently needed to benefit these patients.

Our previous research found that pathways in tumor were significantly affected in pNENs and liver metastases and EGFR tyrosine kinase inhibitor resistance and transcriptional dysregulation in tumor were unique to liver metastasis through KEGG pathway analysis; Meanwhile, GO Biological Processes analysis emphasizes those signaling pathways closely related to tyrosine phosphorylation, DNA repair, and cell cycle regulation, especially in liver metastases. Xiao et al. found that epidermal growth factor receptor (EGFR) was enriched in high glycosylation pNENs using RNA-seq. EGFR was expressed in 21.2% of pNENs using immunohistochemistry and associated with poor overall survival. Therefore, the study from Xiao et al. demonstrates that EGFR may be a potential therapeutic target for pNENs. This is consistent with our previous findings that the EGFR signaling pathway plays an important role in pNENs with liver metastases.

Due to the heterogeneity and complexity of tumors, the efficacy of monotherapy or blocking a single signaling pathway may be limited or this treatment method may easily develop drug resistance. The existing anti-tumor targeted drugs block tumor angiogenesis by inhibiting vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Colony-stimulating factor 1 receptor (CSF1R) is an important signaling pathway associated with the survival and function of tumor associated macrophages (TAMs). Inhibiting CSF1R can regulate the activity of macrophages, improve the immune microenvironment, promote immune response, and activate the body's immune function. Sofantinib is a novel oral tyrosine kinase inhibitor which exerts dual effects of anti-tumor angiogenesis and immune regulation by targeting VEGFR, FGFR1, and CSF1R, resulting in synergistic anti-tumor activity. In December 2020 and June 2021, sorafenib was approved in China as a monotherapy for unresectable locally advanced or metastatic, well differentiated extrapancreatic and pancreatic neuroendocrine neoplasms.

However, in a multicenter, single blind, open label, phase Ib/II clinical trial, the objective response rate for pNENs patients was only 19%. There is currently no effective treatment available for patients with disease progression or drug resistance after undergoing existing treatment regimens. Therefore, there is an urgent need to seek new treatment methods to improve the therapeutic effect of pNENs. Based on our previous research results and relevant literature reports, we speculate that the combination of sorafenib and EGFR inhibitor gefitinib may improve the therapeutic effect of pNENs patients.

Pancreatic ductal adenocarcinoma is the fourth cause of death in the Western world. About 40% of pancreatic cancer patients were diagnosed as locally advanced unresectable status without distant metastasis. Concurrent chemoradiotherapy (CCRT) was a reasonable treatment modality for locally advanced pancreatic cancer. However, several adverse events of chemoradiation could lead unfavorable treatment results, which included unique gastrointestinal (GI) toxicities, such as ulcer and hemorrhage in the stomach and duodenum that are included in the radiation field. According to the study in the investigators hospital, 45% of locally advanced pancreatic cancer patients treated with CCRT suffered from GI ulcers, and among them, 65% of the patients experienced the significant hemorrhage events. Although these GI toxicities, the studies for radioprotective agents were limited. Albis® is a newly developed drug comprised of ranitidine, bismuth and sucralfate. The investigators will investigate the radioprotective effect of Albis® for locally advanced pancreatic cancer patients treated with CCRT.

This prospective cohort, phase II, trial is studying induction chemotherapy combination, FOLFIRINOX regimen, consisted of oxaliplatin, irinotecan, leucovorin and fluorouracil (5-FU), for 4 cycles, followed by consolidation concurrent radiotherapy with capecitabine in non-progressed cases, in treating patients with locally advanced cancer pancreas.

There are doubts concerning the possible benefits derived from the insertion of double-pigtail plastic stents (DPS) within the lumen-apposing metal stents (LAMS) in the EUS-guided transmural biliary drainage (BD). The aims was to evaluate the safety of LAMS with and without a coaxial DPS in EUS-BD for the palliative management in malignant biliary obstruction.

All patients referring to the U.O .of Digestive Endoscopy of the Humanitas Hospital to undergo EUS with biopsy in the pre-treatment evaluation of locally advanced pancreatic adenocarcinoma, satisfying all the inclusion criteria and without any of the exclusion criteria, will be enrolled.

Patients will then undergo endoscopic procedures (EUS with biopsy) provided by good clinical practice in consideration of the suspected diagnosis for which they come to Investigator's attention.

Biopsy will be performed using a histology needle (22 G, Acquire, Boston Scientific, MA, United States). The obtained material will be processed in the Pathological Anatomy. A small part of this will be sent to the NGS analysis.

At the time of preparation for the examination, the patients will be asked for blood collection (10 ml of blood) in order to evaluate any circulating tumor cells that will be identified by SmartBioSurface technique (Tethis S.p.A) and analyzed by appropriate molecular markers and NGS.

The clinical evaluation of the patient will take place at 6 months from the date of the procedure, through telephone contact and / or outpatient visit.

Primary objective:

* To evaluate overall response rate (based on RECIST criterion)

Secondary objective:

* To evaluate time to progression, clinical benefit, quality of life and safety

The purpose of this study is to evaluate the safety and tolerability and determine the recommended dosing for the treatment in patients with advanced pancreatic cancer after fist-line Gemcitabine treatment failure.