Locally Advanced Pancreatic Ductal Adenocarcinoma

The purpose of this study is to evaluate the safety and efficacy of samuraciclib in patients with localized pancreatic cancer.

The purpose of this study is to evaluate the safety and efficacy of samuraciclib in patients with localized pancreatic cancer.

This phase I/II study tests how well zimberelimab and quemliclustat work in combination with chemotherapy (mFOLFIRINOX) in treating patients pancreatic adenocarcinoma that may or may not be able to be removed by surgery (borderline resectable) or that has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as zimberelimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Quemliclustat acts as a blocker for adenosine. Adenosine is a chemical produced in the body that can lead to a decrease in the immune system's response towards cancer. Quemliclustat has the potential to decrease the amount of adenosine, allowing the immune system to recognize and act against the cancer. Chemotherapy drugs, such as oxaliplatin, irinotecan, leucovorin, and fluorouracil, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy in combination with zimberelimab and quemliclustat may kill more cancer cells than chemotherapy alone.

The purpose of this study is to assess the safety, tolerability and efficacy of XER-001 and identify a best dose for future studies.

This early phase I trial studies the biological activity of OMO-103 in patients with pancreatic ductal adenocarcinoma that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). OMO-103 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial may help researchers determine how exposure to OMO-103 changes pancreatic tumor cells.

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.

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.

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.

This study evaluates an investigational scan called hyperpolarized carbon-13 pyruvate magnetic resonance imaging (MRI) in assessing treatment response in patients with pancreatic ductal carcinoma (PDA) that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). MRI is a standard scan that helps doctors see tumors, organs, tissue, and bone. Standard contrast agents (e.g., gadolinium) are sometimes used to help make the scan images brighter, or easier to see. Hyperpolarized carbon-13 pyruvate is an experimental contrast agent that is different from standard MRI contrast in that it provides information on how a tumor processes nutrients. Hyperpolarized carbon-13 pyruvate MRI scans may work better than MRI with standard contrast agents in predicting how PDA tumors respond to treatment.

This study is a single-arm phase II clinical trial. The study targets patients aged 18-75 years with ECOG performance status 0-2, diagnosed with locally advanced pancreatic ductal adenocarcinoma based on comprehensive assessment of pathology and imaging studies (CT or MRI). Participating patients will receive the GnP regimen every 21 days (nab-paclitaxel 125mg/m² ivgtt on days 1 and 8 + gemcitabine 1000mg/m² ivgtt on days 1 and 8, repeated every 21 days) combined with serplulimab (200mg ivgtt Q3W). In the second cycle, patients will receive SBRT targeting the primary tumor and/or retroperitoneal lymph nodes: 6.6Gy×5 fractions, 7Gy×5 fractions, or 8Gy×5 fractions, administered every other day with radiotherapy completed in 5 sessions (specific selection determined by investigators based on lesion size and organs at risk \[OAR\] assessment). Comprehensive evaluation including tumor markers and CT scans will be performed every 2 cycles with multidisciplinary team (MDT) review, and patients who meet surgical criteria will undergo radical resection surgery.

A prospective, single-arm, exploratory phase II clinical study evaluating the efficacy of Gemcitabine and Nab-palitaxe combined with Cadonilimab sequential short-course radiotherapy in the treatment of patients with locally advanced pancreatic ductal adenocarcinoma.