Archives: Clinical Trials

The investigators create organoid from the pancreatic cancer tissue obtained via EUS-FNA and EUS-FNB within the pancreatic cancer diagnostic process. And also the investigators create organoid from the pancreatic cancer tissue obtained after surgery as part of the pancreatic cancer treatment process. Check for the reactivity to anti-cancer drugs through cell viability assay after treating with various anti-cancer drugs, such as anti-cancer drugs used as adjuvant chemotherapy for pancreatic cancer to the organoid. Also, perform genomic analysis on each organoid, and then check if there are any unique genomic mutations for each organoid. By recognizing the relationship between the unique genomic mutations and reactivity to the anti-cancer drug within pancreatic cancer patients eligible for surgery, the investigators aim to strategize appropriate adjuvant chemotherapy after surgery, thus developing a platform to predict the outcomes of each patient.

This study aims to evaluate the clinical value of a structured nutritional support program for patients with pancreatic cancer undergoing CyberKnife radiotherapy. The study compares a sequential nutrition intervention, guided by nutritional risk screening, against routine nutritional advice. The goal is to determine if the structured intervention can better improve patients' nutritional status, immune function, and quality of life, while reducing the rate of postoperative complications.

In light of this new technology and preliminary findings of low toxicity of online, adaptive, magnetic resonance (M)-guided stereotactic radiation on a single arm prospective study, the investigators propose to compare this technique to online MR-guided stereotactic body radiation therapy (SBRT) without adaptation. Online plan adaptation increases treatment times for patients and comprises an increased burden on technical and clinical staff. Although preliminary trial results are encouraging, it remains unclear if the dosimetric benefits of online-adaptive planning studies will translate to measurable improvements in clinical outcomes that merit its routine use. In our preliminary study, plan adaptation was most often required when tumors were adjacent to the gastrointestinal tract (the esophagus to the sigmoid colon), as those structures were most commonly the dose-limiting structures and were noted to change in location on a day-to-day basis. For these reasons, abdominal disease sites have historically highlighted the limitations of SBRT. Specifically, the investigators will enroll patients with oligometastatic or unresectable primary disease of the non-liver abdomen to a randomized, prospective trial.

Patients will be randomized to one of two treatment arms, in which they will receive either online-adaptive, MRI-guided SBRT or non-adaptive MRI-guided SBRT. Both patient groups will undergo MRI simulation and MRI treatment localization with online MR monitoring and/or gating. All patients will be treated in five fractions over one to two weeks. By adhering to strict normal tissue constraints, the investigators expect toxicity to be within the current standard of care for the non-adaptive arm, with reduction in toxicity in the arm of patients who undergo adaptation based on daily anatomic changes.

This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of the orally administered phosphatidylinositol 3'-kinase (PI3K) inhibitor BKM120 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) which has progressed on EGFR inhibitors and triple negative breast cancer, as well as pancreatic cancer, colorectal cancer, malignant melanoma, NSCLC, and other advanced solid tumors with KRAS, NRAS, and/or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RP2D, two expansion arms will be opened in order to further assess safety and preliminary anti-tumor activity of the combination of BKM120 and MEK162.

Study drugs will be administered once daily orally on a continuous schedule. A treatment cycle is defined as 28 days.

Pancreaticoduodenectomy (PD) is a complex procedure performed in patients with malignant or benign tumors of the pancreatic head and periampullary region, associated with high morbidity and mortality. Postoperative pancreatic fistula (POPF) is the most common and clinically significant complication following PD. In this study, the investigators aim to determine the predictive risk factors for clinically related postoperative pancreatic fistula (CR-POPF) in the preoperative, intraoperative and postoperative period in patients that underwent PD. The total number of 100 participants expected to be included in this research who underwent PD between 2025 and 2026.

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.

The aim of high dose radiotherapy treatment is to deliver enough radiation to the tumour to kill all the cancer cells while at the same time giving a low dose of radiation to the normal parts of the body to reduce the side effects of treatment. This requires the cancer specialist to accurately identify the areas of cancer on a computed tomography (CT) scan. Positron emission tomography computed tomography (PETCT) scans use radioactive sugar that is injected into the patient. This sugar goes into cancer cells and shows up as a bright spot on the PET scan, allowing the doctors to see tumours more accurately. Some cancers move with breathing, for example lung, pancreas and oesophageal (or gullet) cancers. Fourdimensional CT scanning (4DCT) is a special type of CT scan that allows the motion of the tumour to be seen and measured accurately. This information can then be used to help ensure that the radiotherapy correctly treats the moving tumour.

The aim of this study is to see if there are possible benefits to combining PET with 4DCT to get a 4D PETCT scan for tumours that move with breathing. This study is divided into three cancer types; lung, lower oesophagus and pancreatic cancer.

First the investigators are going to test the use of 4D PETCT in the radiotherapy planning of these tumours to see if it helps the doctor to identify the cancer.

Secondly, the investigators are going to see if the 4D PETCT helps to show areas within the cancer that are potentially more active. This might then allow us to target a higher dose to these areas, which could potentially improve the chance of controlling and curing the cancer. Patients' standard treatment will not be altered by participating in the study.

This is an open label, randomized phase 2 study of NaliCap (irinotecan liposome/Capecitabine) compared to NAPOLI (irinotecan liposome/5-FU/LV) in gemcitabine-pretreated advanced pancreatic cancer patients.

The purpose of this study is to determine the safety and the efficacy of the combination of the drugs TH-302 and sunitinib in metastatic neuroendocrine tumours.

The primary objectives of Part 1 of this study are to:

* Assess the safety and tolerability of the combination of BGB-3245 and panitumumab in participants with advanced or metastatic colorectal cancer (CRC) with a known mutation status and tumor harboring an oncogenic mutation of v-Raf murine sarcoma viral oncogene homolog B; B-RAF proto-oncogene, serine/threonine kinase (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), or neuroblastoma RAS viral oncogene homolog (NRAS) with documented disease progression during or after at least 1 line of prior therapy.
* Determine the maximum tolerated dose (MTD) of BGB-3245 in combination with panitumumab and the recommended phase 2 dose (RP2D) of the combination.

The primary objective of Part 2 of this study is to determine the objective response rate (ORR) as assessed by initial investigator review using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with BGB-3245 and panitumumab combination treatment at the RP2D.