Clinical Research Directory

NALIRIFOX Before Surgery for the Treatment of Borderline Resectable Pancreatic Ductal Adenocarcinoma, Nectar Trial

This phase II trial tests how well liposomal irinotecan, oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) before surgery works in treating patients with pancreatic ductal adenocarcinoma that is close to major blood vessels, but is still potentially removable by surgery (borderline resectable). Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Liposomal irinotecan is a form of the anticancer drug irinotecan that is contained inside very tiny, fat-like particles. Liposomal irinotecan may have fewer side effects and work better than other forms of the drug. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill tumor cells. 5-fluorouracil, a type of antimetabolite, stops cells from making DNA and it may kill tumor cells. Leucovorin, a form of folic acid, is used to lessen the toxic effects of substances that block the action of folic acid. It is a type of chemoprotective agent and a type of chemosensitizing agent. Giving NALIRIFOX before surgery may improve the chance of successful surgery and decrease the chance of the cancer returning after surgery in patients with borderline resectable pancreatic ductal adenocarcinoma.

Targeted Pathway Inhibition in Patients With Pancreatic Cancer

This early phase I trial aims to determine how cobimetinib, olaparib, onvansertib, azenosertib, AZD5305 or tremelimumab works in patients with pancreatic cancer. Validation of cobimetinib, olaparib, onvansertib azenosertib, AZD5305 and tremelimumab molecular targets will be explored by comparing pre-treatment biopsies with post-treatment specimens. This knowledge will help design future biomarker driven trials to determine whether giving cobimetinib, or olaparib, or onvansertib or azenosertib, or AZD5305, or tremelimumab will work better than standard treatments in patients with pancreatic cancer.

Using Tumour DNA and Proteins to Better Understand How Pancreatic Cancer Responds to Treatment

The goal of this study is to learn if the genetic information and proteins from tumours can help treat pancreatic ductal adenocarcinoma (PDAC). The main questions it aims to answer are: * Is it feasible to obtain genetic test results within a timeframe that can help inform treatment decisions for individuals with PDAC? * Can the genetic test results provide information about how a tumour will respond to or resist treatment? Participants will: * Receive standard chemotherapy to treat their cancer. * Provide samples of their blood, tissue, and fluid for genetic testing. * Visit the clinic every 4 weeks for check-ups and tests. * Complete questionnaires every 12 weeks.

PULSAR in Systemic Therapy for Pancreatic Cancer

Pancreatic cancer remains one of the malignancies with the lowest survival rates, largely due to late-stage diagnosis and the difficulty of achieving curative resection. A substantial proportion of patients present with locally advanced, unresectable disease at the time of diagnosis, making intensive systemic therapy the current standard of care. For selected patients, radiation therapy (RT) is integrated to improve local control. Local progression in the pancreas can lead to severe complications, including intractable pain, gastric outlet obstruction, and biliary obstruction, which ultimately contribute to morbidity, deteriorating quality of life, and reduced overall survival. Therefore, effective local therapy remains a critical component of comprehensive management. However, delivering high-dose radiation to pancreatic tumors is particularly challenging because the pancreas is anatomically surrounded by radiation-sensitive organs such as the stomach, duodenum, liver, kidneys, and small bowel. Conventional RT and stereotactic body RT (SBRT) have both been limited by gastrointestinal toxicity, making substantial dose escalation difficult and resulting in modest local control outcomes. Previous studies combining systemic therapy with radiotherapy have shown signals of improved local progression-free survival (LPFS) and progression-free survival (PFS). Still, results have been inconsistent across trials, highlighting the need for rigorous clinical evaluation of the true therapeutic benefit of integrating radiotherapy with systemic treatment in this disease population. Conventional RT often requires several weeks of treatment, during which interruption or modification of systemic therapy may increase the risk of distant progression. SBRT shortens the treatment duration but exposes patients to large per-fraction radiation doses, increasing the risk of gastrointestinal injury and limiting eligibility to highly selected cases. Against this backdrop, the recently proposed PULSAR (Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy) strategy offers an innovative approach to overcome the limitations of traditional radiation therapy. PULSAR delivers 3-4 ultra-fractionated, stereotactic "pulses" of radiation at intervals of approximately 3-4 weeks. Each pulse is delivered with adaptive planning based on interval changes in tumor anatomy and nearby organs at risk. This wide spacing minimizes interruptions to systemic therapy and provides time for tumor shrinkage and normal tissue recovery before subsequent pulses. These features may reduce toxicity while enabling more effective dose delivery to the tumor. Such advantages are particularly relevant for pancreatic tumors located adjacent to sensitive gastrointestinal structures, potentially improving upon the limitations of SBRT. The proton beam therapy offers additional precision through the physical characteristics of proton beams, particularly the Bragg peak, which allows for high-dose deposition within the tumor while sparing surrounding normal tissues. The combination of proton therapy with the PULSAR framework may provide a highly targeted, organ-preserving local treatment strategy for a disease known for its complex anatomy and therapeutic difficulty. Within this context, a clinical strategy that integrates intensive first-line systemic therapy followed by PULSAR-based adaptive proton radiotherapy holds promising potential. Systemic therapy may reduce tumor burden, after which personalized, pulse-based proton irradiation can be tailored according to treatment response, delivering biologically effective doses to maximize local control while maintaining systemic treatment intensity. This approach may enhance survival outcomes by addressing both local disease control and risk of distant metastasis. In summary, given the critical need to improve survival in locally advanced pancreatic cancer and the inherent limitations of existing radiation approaches, combining PULSAR-guided adaptive proton therapy with contemporary systemic therapy represents a compelling new treatment paradigm. This study aims to systematically evaluate the clinical feasibility, safety, and therapeutic effectiveness of this integrated approach in patients with locally advanced pancreatic cancer.

Determining the Link Between Dietary Patterns, Fecal Microbiome and Response to Neoadjuvant Chemotherapy

This study explores the relationship between pre-treatment dietary patterns, fecal microbiome, and response to chemotherapy in patients with pancreatic ductal adenocarcinoma.

Gemcitabine, Cisplatin and Nab-Paclitaxel as Neoadjuvant Treatment for Patients With Resectable or Borderline Resectable Pancreatic Cancer

This phase II trial tests how well gemcitabine, cisplatin and nab-paclitaxel given before surgery (neoadjuvant) works in treating patients with pancreatic cancer that can be removed by surgery (resectable) or that is borderline resectable. The standard treatment for resectable and borderline resectable pancreatic cancer is a combination of surgery and chemotherapy. Neoadjuvant therapy has been shown to improve overall survival compared to patients receiving surgery first. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel, an antimicrotubule agent that stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel may have fewer side effects and work better than other forms of paclitaxel. Gemcitabine, cisplatin and nab-paclitaxel may be an effective neoadjuvant treatment option for patients with resectable or borderline resectable pancreatic cancer.