Clinical Research Directory

Cost-utility Evaluation of Cytoreductive Surgery With or Without Mitomycin-C Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Resectable Colorectal Peritoneal Metastases

Colorectal cancer is the second leading cause of cancer death in France, with close to 50,000 new cases each year. About half of the patients develop liver, lung and/or peritoneal metastases during the course of the disease.Peritoneal involvement, which accounts for approximately 8,000 new cases per year, carries the poorest prognosis, notably because of its chemoresistance.For patients with resectable colorectal peritoneal metastases,recommended optimal management combines systemic chemotherapy with complete cytoreductive surgery(CRS)in an expert center.Hyperthermic IntraPeritoneal Chemotherapy(HIPEC)may be added to CRS to eradicate residual microscopic disease and potentially improve survival.Clinical evidence on HIPEC for colorectal peritoneal carcinomatosis is heterogeneous and dominated by a randomized trial reporting no survival benefit and increased morbidity, results attributed to the oxaliplatin-based HIPEC regimen used. A separate body of evidence suggests a benefit of mitomycin-C-based HIPEC, with manageable morbidity and preserved quality of life. National and international guidelines therefore allow mitomycin-C HIPEC, but the procedure remains controversial: according to French hospital discharge data, about half of the patients treated for colorectal peritoneal carcinomatosis receive CRS plus HIPEC and the other half CRS alone.HIPEC also raises funding and efficiency issues. No specific French diagnosis-related tariff (GHS)exists for CRS plus HIPEC, whereas the procedure is costly in terms of operating time,human and material resources, and is associated with prolonged hospital stays and complications. To date, no prospective comparative data on the efficiency of CRS plus HIPEC are available in France.ECO-CHIP is a national,multicenter, prospective, comparative,non-randomized, open, non-interventional study using a " here-elsewhere " design (French RIPH category 3). Each participating center follows its own routine practice: centers performing HIPEC treat included patients with CRS plus mitomycin-C HIPEC (innovative strategy), while centers not performing HIPEC treat included patients with CRS alone (reference strategy).No change in management, examination or procedure is imposed by the protocol.the only procedure added because of the research is the completion of self-administered questionnaires (EQ-5D-5L, EORTC QLQ-C30, EORTC QLQ-CR29 and PERI-PROM) at inclusion and at months 1, 3, 6, 12, 18, 24 and 36 after cytoreductive surgery. The primary objective is to assess, from the French health care system perspective and over a 36-month horizon, the efficiency (cost-utility) of cytoreductive surgery combined with mitomycin-C HIPEC versus cytoreductive surgery alone. Costs are derived from micro-costing of the index hospital stay and from individual linkage with the French National Health Data System(SNDS); utilities are derived from the EQ-5D-5L using the French value set. Secondary objectives compare the two strategies in terms of disease-free survival, peritoneal recurrence-free survival, overall survival, toxicity, postoperative complications, recurrence patterns, access to iterative complete cytoreduction, costs, budget impact for the French statutory health insurance, cost-effectiveness at 3 and 5 years, and health-related quality of life. Study hypothesis: the addition of mitomycin-C HIPEC to complete cytoreductive surgery is an efficient strategy for the French health care system, improving disease-free survival (expected 3-year disease-free survival of 26% with CRS plus HIPEC versus 13% with CRS alone, hazard ratio 0.66) and quality-adjusted survival at an acceptable incremental cost per QALY gained. perspective and over a 36-month horizon, the efficiency (cost-utility) of cytoreductive surgery combined with mitomycin-C HIPEC versus cytoreductive surgery alone. Costs are derived from micro-costing of the index hospital stay and from individual linkage with the French National Health Data System (SNDS); utilities are derived from the EQ-5D-5L using the French value set. Secondary objectives compare the two strategies in terms of disease-free survival, peritoneal recurrence-free survival, overall survival, toxicity,postoperative complications, recurrence patterns, access to iterative complete cytoreduction, costs, budget impact for the French statutory health insurance, cost-effectiveness at 3 and 5 years, and health-related quality of life. Study hypothesis: the addition of mitomycin-C HIPEC to complete cytoreductive surgery is an efficient strategy for the French health care system, improving disease-free survival(expected 3-year disease-free survival of 26% with CRS plus HIPEC versus 13% with CRS alone,hazard ratio 0.66)and quality-adjusted survival at an acceptable incremental cost per QALY gained.A total of 398 patients 199per group are planned for inclusion in French digestive and surgical oncology departments over a 36-month enrolment period, each patient being followed for 36 months

Isunakinra Alone and in Combination With Pembrolizumab in Patients With Colorectal Cancer (MSS)

This study will enroll patients with colorectal cancer that is locally advanced or metastatic. The tumor must be microsatellite stable (MSS), have a tumor mutational burden that is high (TMB-H) and be kras mutated. Patients must have been treated with available approved treatments already. In this study the investigators are testing a new type of immunotherapy, the potent IL-1 inhibitor isunakinra to be added to already approved immunotherapy (PD-1/PD-L1 inhibitor) in an attempt to get this treatment to work in this treatment resistant type of tumor.

Improving Outcome of Selected Patients With Non-resectable Hepatic Metastases From Colo-rectal Cancer With Liver Transplantation

The COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial, aimed at assessing the efficacy (in terms of overall survival: OS) of liver transplantation (LT) in liver-only CRC metastases, compared with a matched cohort of patients bearing the same tumor characteristics, collected during the same time period and included in a phase III Italian RCT on triplet chemotherapy+antiEGFR

EO4010 in Previously Treated Metastatic Colorectal Carcinoma

Open-label multicenter study

Medical Cannabis in Patients With Advanced Pancreatic and Colorectal Cancer

Many patients with advanced pancreatic cancer and colorectal cancer experience burdensome and difficult-to-treat symptoms. The impact of multiple symptoms (called "symptom burden") can negatively affect a patient's quality of life, decrease their ability to tolerate cancer treatments, and lead to worse survival. Current approaches to manage these cancer-associated symptoms often work poorly, with most patients reporting a moderate to severe symptom burden. Therefore, there is an urgent need for treatments that improve these symptoms in patients with advanced pancreatic and colorectal cancer, and data suggests that medical cannabis can help. In this research study, we are examining the usefulness of using medical cannabis in patients with advanced pancreatic cancer and colorectal cancer to further study how cannabis can impact their symptom burden.

Therapeutic Efficacy and Safety of Ultrasound-Guided Microwave Ablation for Hepatic Metastatic Nodules

The liver is one of the most common organs where cancer cells spread (metastasize) from other parts of the body, especially from gastrointestinal cancers such as colorectal cancer. While surgical removal of liver tumors has traditionally been the standard treatment, most patients are not candidates for surgery due to tumor location, number of lesions, or underlying liver function. For these individuals, minimally invasive local therapies such as microwave ablation (MWA) provide an alternative approach to eradicate tumor tissue while preserving healthy liver parenchyma. Microwave ablation delivers localized high-frequency electromagnetic energy through a thin needle antenna placed percutaneously into the liver tumor. The generated heat induces rapid coagulative necrosis, destroying cancer cells within the target area. In this study, real-time ultrasound combined with CT image-fusion navigation is used to precisely position the ablation antenna within each nodule. The primary purpose of this study is to assess the therapeutic efficacy and safety of ultrasound-guided percutaneous microwave ablation for patients with liver metastases. Participants receive microwave ablation for their target liver tumors and are evaluated with contrast-enhanced CT or MRI at 1 month post-procedure to determine the rate of complete tumor ablation. Patients are then monitored longitudinally at 3, 6, 9, and 12 months to evaluate safety and check for local tumor recurrence.

STREAM-2: Second-line Treatment With REgorafenib in Advanced RAS-Mutant Colorectal Cancer

The investigators hypothesize that patients with mCRC RAS-mutant eligible for a second line treatment with good prognostic features, identified as single metastatic site, long progression free survival (PFS) in first line treatment, might benefit from a personalized approach, with less intensive treatment with regorafenib as part of a continuum-of-care strategy aimed at ensuring quality of life and extending survival.

Comparison of Molecular-Genetic Concordance of the Primary Tumor and Brain Metastases of Colorectal Cancer

GENCONCOR-1 study is translational research aimed to investigate the concordance of the molecular genetic profile of the primary tumor and brain metastases (BM) of colorectal cancer (CRC). The study was conducted by post hoc analysis of pairs of samples of histological material with determination of the mutational status of genes KRAS, NRAS, BRAF, HER2 and MSI.

In Vivo Lung Perfusion (IVLP) for Colorectal Cancer Metastatic to Lung

This study is investigating a new technique for delivering chemotherapy directly into the lungs at the time of surgery. Delivering chemotherapy directly to the lungs could potentially kill any microscopic cancer cells that are present in the lungs at the time of surgery, while sparing other major organs in the body from the side effects of chemotherapy. This technique is called In Vivo Lung Perfusion (IVLP). At the University Health Network, this IVLP technique has been used recently in a Phase I study in patients with sarcoma, and we are now expanding on that experience to include patients with colorectal metastases. The purpose of this study is to test the safety of the IVLP technique and find the dose that seems right in humans. Participants are given oxaliplatin into one lung via IVLP and are watched very closely to see what side effects they have and to make sure the side effects are not severe. If the side effects are not severe, then more participants are asked to join the study and are given a higher dose of oxaliplatin. Participants joining the study later on will get higher doses of oxaliplatin than participants who join earlier. This will continue until a dose is found that causes severe but temporary side effects. Doses higher than that will not be given. The other lung will not be infused with anything, so that we can limit unforeseen toxicity to a single lung and see if one lung does better than the other.

Comprehensive Genomic Profiling of Colorectal Cancer Patients With Isolated Liver Metastases to Understand Response & Resistance to Cancer Therapy

This is a prospective study investigating the disease course of patients with colorectal cancer that have had their cancer spread to their liver. The aim of this study is find potential biomarkers for disease recurrence and therapeutic targets for prognostic information.

Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

This is a multicenter, randomized, open-label, Phase 3 study

XNW27011 Study of Advanced Solid Tumor Subjects Who Failed Standard Therapies.

This is a global, multi-center, open-label, Phase I/II first-in-human study of XNW27011 monotherapy as an investigational product (IP) in patients with locally advanced and/or metastatic solid tumors who have failed or are intolerant to standard therapies. XNW27011 is an antibody-drug conjugate (ADC) targeting Claudin 18.2 (CLDN18.2), a transmembrane protein important to tight junctions. The study consists of 2 parts: Part 1 is the dose-escalation phase (Phase I), and Part 2 is the does-expansion phase (Phase II). In phase I part of the study, approximately 42 patients with locally advanced and/or metastatic solid tumors will be enrolled, irrespective of CLDN18.2 expression. However, the most recently available tumor tissue specimen will be collected (if available) for a retrospective CLDN18.2 expression confirmation. In phase II part of the study, only patients with confirmed CLDN18.2 expression by IHC in the central laboratory will be enrolled.The phase II part of the study will consist of the following four groups，Up to three dose cohorts for each patient group are planned currently. Each dose cohort will include approximately 20 patients. Approximately 240 patients evaluable will be enrolled in Phase Ⅱ part of the study.

BAL/BOT/agenT-797 in pMMR CRC With Liver Metastases

The goal of this clinical trial is to learn whether the combination of balstilimab, botensilimab, and agenT-797 is safe and effective in treating adults with previously treated metastatic colorectal cancer that is microsatellite stable (pMMR) and has spread to the liver. The main questions it aims to answer are: * What proportion of participants experience tumor shrinkage (objective response rate) based on imaging assessments? * What side effects occur with this combination treatment, including immune-related and cytokine-related reactions? All participants in this study will receive the combination treatment. There is no comparison group. Participants will: * Receive balstilimab, botensilimab, and agenT-797 in repeating 42-day treatment cycles * Undergo imaging scans (such as CT or MRI) to assess tumor response * Have blood samples collected to monitor safety and evaluate biomarkers * Provide tumor tissue samples for research * Be monitored for side effects throughout the study * Participate in follow-up visits to assess survival after treatment completion

Safety and Activity of PolyPEPI1018 Plus Atezolizumab in Colorectal Cancer.

This is a multicenter, open label, phase II trial to determine the safety, tolerability, and immunogenicity and initial clinical activity of the combination treatment of PolyPEPI1018 vaccine and atezolizumab in participants with MSS CRC who have progressed on 2 or 3 prior regimens.

Quality of Life After Cytoreductive Surgery and Intraperitoneal Chemotherapy

Cytoreductive surgery with intraperitoneal chemotherapy is one of the most important treatments for patients with colorectal cancer and peritoneal metastasis. For the best survival rates, complete removal of all metastatic lesions is the most important part of treatment, and various surgical procedures are required for the complete cytoreduction. Therefore, the postoperative morbidity rates are higher than those of localized colon cancer surgeries and patients can experience a prolonged recovery period and deterioration of physical activities over a long period. The aim of this study is to investigate the change of quality of life after cytoreductive surgery and intraperitoneal chemotherapy for colorectal cancer.

Continuous or Intermittent Cetuximab Plus FOLFIRI as First-line Treatment in RAS/BRAF Wild-type mCRC Patients

The goal of this clinical trial is to learn if the application of the chemotherapy FOLFIRI and cetuximab works better when given with scheduled breaks or continuously in adults with metastatic colorectal cancer. The main question it aims to answer is, whether worsening of disease after 12 months of treatment is lower when the treatment is given with breaks or given continuously. It will also answer the question whether the quality of life is better and side effects are less if chemotherapy is given with breaks. Additionally, the treatment breaks will be controlled by blood tests and imaging examinations. A novel blood test will be introduced to investigate, whether worsening of the disease might be detected before the imaging, and whether a quicker reaction by re-starting the therapy would help the patients. Participants will: * receive an established chemotherapy mit FOLFIRI and cetuximab * Receive blood tests every 4 weeks and imaging investigations every 12 weeks * fill out questionnaires to report their quality of life

FOLFIRI Plus Bevacizuamb and QL1706 in Second-Line Treatment for mCRC

Thsi study is a randomised, parallel-controlled phase II/III trial evaluating FOLFIRI plus bevacizumab with or without QL1706 as second-line therapy for metastatic colorectal cancer. The primary endpoint is PFS. Secondary endpoint includes overall survival, objective response rate, safety profiles, immune-related adverse events, and patient quality of life. Exploratory analyses focus on dynamic shifts in tumour immune microenvironment and biomarkers, aiming to identify predictive signatures for therapeutic efficacy and immune toxicities.

Living Donor Liver Transplant for Unresectable Colorectal Liver Metastases

The goal of this study is to create a data registry to capture clinical, pathologic, and molecular data/outcomes for patients with metastatic colorectal cancer who undergo live donor liver transplantation.

SHR-A1904 in Advanced Colorectal Cancer: an Exploratory Study

To evaluate the safety and efficacy of SHR-A1904 in the advanced colorectal cancer after failure of standard therapy

Galunisertib Combined With Capecitabine in Advanced CRC With PM

This is a two-center open-label non-randomized proof of principle study consisting of a dose-finding part (phase I) and phase II study with Simon two-stage design investigating the anti-tumor activity of the combination of capecitabine and galunisertib in patients with colorectal cancer with peritoneal metastases.

Registry Platform Colorectal Cancer

The registry aims to collect and analyse information on the antineoplastic treatment of patients with metastatic colorectal cancer, treated in palliative intention in daily routine practice in Germany.

A Phase II Clinical Study of Multimodal Ablation Combined With Systemic Drug Therapy for Advanced Solid Tumors.

This study focuses on the treatment of liver metastases from three common cancers: colorectal cancer, triple-negative breast cancer and melanoma. Currently, there are limitations in the treatment of liver metastases of these cancers. Multimodal thermophysical ablation therapy can reshape the tumor microenvironment, release neoantigens, and act as an in-situ vaccine. On this basis, the combination of multimodal ablation with immunotherapeutic drugs such as pucotenlimab will be explored. The efficacy and safety of this combination therapy in patients with liver metastases of solid tumors will be investigated, with the expectation of breaking through the existing treatment limitations.

Colorectal Metastasis to Liver Extraction With Auxiliary Transplant and Delayed Resection

Liver transplantation (LT) has become an accepted treatment for selected patients with unresectable liver metastases due to colorectal cancer (CRLM). The goal of this study is to look at and compare the clinical results of all the different approved methods (living vs. Deceased, whole organ vs. Split, one staged vs. Two staged) used to perform a standard liver transplant procedure for recipients with CRLM. Investigators will look at things like different procedure results, recovery in the hospital, and survival rates one year after the transplant. Investigators will also take blood samples from participants to be used in future research. All the transplant methods the investigators are comparing are standard practices approved by the United Network of Organ Sharing (UNOS).

Pilot Study of an Implantable Microdevice for In Situ Evaluation of Drug Response in Patients With Colorectal Liver Metastasis

Microdevices have been used to ascertain in vivo drug response, which can lead to improved cancer treatment delivery; however, they have not been evaluated for liver tumors. This is a prospective, phase 1 safety study of percutaneous placement and surgical retrieval of a microdevice in patients with liver metastasis from colorectal cancer. The device will be implanted percutaneously 3-5 days prior to scheduled resection of colorectal liver metastasis (CLM) and then removed en bloc with the tumor. Patients will be monitored to ensure that the device's placement and retrieval does not result in increased complication rates within 14 days of surgery. To assess feasibility, the tissue surrounding the microdevice will be analyzed to assess the diffusion of the drugs from the device into the tissue and whether the therapeutic effect of diffusing chemotherapy +/- immune-modulating drugs has an impact on the surrounding tissue.