Colorectal Adenocarcinoma

The goal of this clinical trial is to determine the safety and efficacy of of ACM-CpG for inoperable peritoneal metastases or malignant ascites. The main questions it aims to answer are: • To determine the safety and maximum tolerated dose (MTD) or optimal biologic dose (OBD) of intraperitoneal injection(s) of ACM-CpG for inoperable peritoneal metastases or malignant ascites? Researchers will assign treatment levels using escalating doses of ACM-CpG Therapy. Participants will: * Will receive at least one dose of ACM-CpG therapy on Day 1 of a 28-day treatment cycle. * May receive up to 2 additional injections if they have clinically stable or responsive disease. * Must visit the clinic on Days 1, 4, 7, 10, 14, 21, and 28 for checkups and tests. * Will have a CT scan or MRI performed every 8 weeks for 3 scans and then continue to receive scans every 12 weeks to monitor their disease.

This phase I trial tests whether fluoxetine (prozac) works to modify the tumor immune cells before surgery in patients with colorectal cancer. Fluoxetine is a commonly used selective serotonin reuptake inhibitor (SSRI) prescribed for major depressive disorder and generalized anxiety. Giving fluoxetine may modify the immune cell composition in the tumor and its microenvironment and may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread in patients with colorectal cancer.

This clinical trial compares patient (proband)-mediated communication to provider-mediated communication for improving genetic testing in first-degree relatives of patients with newly diagnosed colorectal cancer. It is estimated that 30% of cases of colorectal cancer have a genetic basis and about 15% of these patients have a disease-causing (pathogenic) inherited (germline) variant in a cancer susceptibility gene. Most individuals carrying a pathogenic germline variant are unaware of their cancer risk and may not meet guidelines for genetic testing. Identifying pathogenic germline variants or hereditary cancer syndromes in cancer patients has important implications for their at-risk relatives who may not know that they are at high risk for cancer. The burden of communicating this risk to first-degree relatives often falls on the patients, who may lack sufficient knowledge to correctly share and explain their genetic test results. Receiving provider-mediated communication of genetic testing results may be more effective at communicating genetic risk to first-degree relatives than the usual practice of proband-mediated communication.

The investigators of this study are developing a simple breath test to help detect gastrointestinal (gut) cancers earlier, including cancers of the oesophagus (food pipe), stomach, pancreas, liver and bowel. These cancers often cause non-specific symptoms that are similar to benign conditions, making early diagnosis difficult. Delays between the onset of symptoms and referral for a diagnostic test such as an endoscopy or a scan, can allow the cancer to progress. The breath test detects small molecules called volatile organic compounds (VOCs) that are released in exhaled breath. Some of these VOCs are strongly associated with these cancers and may help identify high-risk patients who require urgent investigation. In practice, patients who come to their GP with concerning symptoms will be offered the breath test. If the test is positive, patients can be referred promptly for a diagnostic test, while those with a negative result can be reassured and offered re-testing if symptoms persist. Earlier diagnosis could improve access to curative treatment while reducing unnecessary invasive investigations. Previous studies have identified a panel of VOCs that appear to distinguish patients with gastrointestinal cancers from those without cancer. This study aims to confirm these findings in a new group of participants to determine whether the same biomarkers can be reliably identified. Participants will provide a breath sample, usually before a hospital procedure they are already scheduled to undergo, and complete a short questionnaire about their medical history and medications. Some participants will also be asked to drink a nutritional supplement before providing a second breath sample. The results will help determine whether the breath test is reliable enough for further clinical evaluation

This study will evaluate the role of mass-based response testing (MRT) to select and deliver personalized hyperthermic intraperitoneal chemotherapy (HIPEC) regimens to patients with peritoneal metastasis (PM) from high-grade appendiceal adenocarcinomas (HGAA) and colorectal cancer (CRC).

This is a first-in-human Phase 1b, 2-part, multicenter open-label clinical study to evaluate safety and efficacy of a Nectin-4 radiopharmaceutical (\[225Ac\]Ac-AKY-1189) in patients with locally advanced or metastatic solid tumors and to establish the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended Phase 2 dose.

Title:A Single-Arm, Single-Center, Phase II Exploratory Study of Serplulimab Combined with Decitabine plus CAPOX as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer Background:Colorectal cancer is one of the most common gastrointestinal malignancies worldwide. Patients with locally advanced colorectal cancer remain at high risk of recurrence and distant metastasis after surgery. Although perioperative chemotherapy has improved clinical outcomes, the pathological complete response rate remains limited. Immune checkpoint inhibitors have shown remarkable efficacy in dMMR/MSI-H colorectal cancer; however, most pMMR/MSS tumors respond poorly to immunotherapy alone. Decitabine, a DNA methyltransferase inhibitor, may enhance tumor immunogenicity by promoting tumor antigen expression, improving antigen presentation, increasing immune cell infiltration, and reshaping the tumor immune microenvironment. CAPOX chemotherapy may further induce immunogenic cell death and enhance antitumor immune responses. Therefore, the combination of serplulimab, decitabine, and CAPOX may provide a synergistic neoadjuvant treatment strategy for locally advanced colorectal cancer. Objective:This study aims to evaluate the efficacy and safety of serplulimab combined with decitabine plus CAPOX as neoadjuvant therapy for patients with locally advanced colorectal cancer. The primary endpoint is pathological complete response rate. Secondary endpoints include R0 resection rate, tumor downstaging, objective response rate, disease-free survival, and safety outcomes. Methods:This is a prospective, single-center, single-arm, phase II exploratory clinical study. A total of 35 patients with previously untreated locally advanced colorectal adenocarcinoma will be enrolled. Eligible patients are adults aged ≥18 years with histologically or pathologically confirmed cT3/cT4N+M0 colorectal adenocarcinoma according to the AJCC/UICC 8th edition, at least one measurable lesion according to RECIST 1.1, ECOG performance status of 0-1, adequate organ function, and an expected survival of more than 3 months. The study includes a safety lead-in stage and a dose-expansion stage. In the safety lead-in stage, decitabine dose escalation will follow a conventional 3+3 design, with two planned dose levels: 10 mg and 15 mg intravenously on Days 1-2 of each 3-week cycle. Serplulimab will be administered at 300 mg intravenously on Day 1 of each 3-week cycle. CAPOX consists of oxaliplatin 130 mg/m² intravenously on Day 1 and capecitabine 1000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle. The maximum tolerated dose or recommended phase II dose of decitabine will be determined based on dose-limiting toxicity. In the dose-expansion stage, patients will receive serplulimab combined with decitabine and CAPOX for four cycles as neoadjuvant therapy. Patients without distant metastasis and considered suitable for surgery will undergo radical colorectal cancer resection 2-4 weeks after completion of neoadjuvant treatment. Postoperative adjuvant therapy will be determined by the investigator according to pathological findings and clinical practice. Endpoints and Analysis:The primary endpoint is pathological complete response, defined as the absence of residual viable tumor cells in the primary tumor and resected lymph nodes after neoadjuvant therapy. Secondary endpoints include R0 resection rate, tumor downstaging rate, objective response rate assessed by RECIST 1.1, and disease-free survival. Safety assessments include adverse events, serious adverse events, immune-related adverse events, laboratory abnormalities, vital signs, 12-lead ECG, ECOG performance status, thyroid function, and physical examination findings. Adverse events will be graded according to NCI-CTCAE version 5.0. Descriptive statistics will be used for analysis. Continuous variables will be summarized by mean, standard deviation, median, minimum, and maximum. Categorical variables will be summarized by frequency and percentage. Time-to-event outcomes will be analyzed using the Kaplan-Meier method. Expected Significance:This study will explore whether the combination of PD-1 blockade, epigenetic modulation, and CAPOX chemotherapy can improve pathological response while maintaining acceptable safety in locally advanced colorectal cancer. The results may provide preliminary evidence for a new neoadjuvant treatment strategy and support future multicenter clinical studies.

This study aims to develop a highly sensitive, specific, and cost-effective blood assay for early detection of colorectal adenomas and cancer, using advanced machine learning and state-of-the-art biological analyses.

Colorectal cancer (CRC) once predominantly affected older individuals, but in recent years has witnessed a progressive increase in incidence among young adults. Once rare, early-onset colorectal cancer (EOCRC, that is, a CRC diagnosed before the age of 50) now constitutes 10-15% of all newly diagnosed CRC cases and it stands as the first cause of cancer-related death in young men and the second for young women. This study aims to detect EOCRC with a non-invasive test, using a blood-based molecular assay based on microRNA (ribonucleic acid)

This study will develop an assay to predict disease recurrence in patients with stage II/III CRC after receiving adjuvant chemotherapy, using genome-wide DNA methylation.

Biotherapies are biological (extracted from an organism or living tissue) or biotechnological drugs used in the treatment of multiple conditions, such as autoimmune inflammatory diseases, cancers, and hematologic diseases. In recent years, these biotherapies have notably emerged in the treatment of cancers and hematologic disorders. As such, most patients with cancers or hematologic diseases will likely receive a biotherapy as part of their care pathway. These biotherapies are associated with various side effects, including hypersensitivity or allergic reactions, which are often poorly characterized in clinical trials. These reactions manifest as symptoms without specific dermatologic or allergologic semiology (such as itching, erythema, shortness of breath, sometimes digestive issues, or discomfort, and in some cases, an anaphylactic reaction). Unlike other treatments, such as antibiotics and neuromuscular blockers, there are currently no guidelines on the concentrations to use in skin tests for biotherapies. We propose conducting prospective clinical research to scientifically establish the concentrations to be used when investigating hypersensitivity to a biotherapy, in line with best practice recommendations for drug skin testing.

The goal of this study is to test autologous logic-gated Tmod™ CAR T-cell products in subjects with solid tumors including colorectal cancer (CRC), pancreatic cancer (PANC), non-small cell lung cancer (NSCLC), ovarian cancer (OVCA), mesothelioma (MESO), and other solid tumors that express mesothelin (MSLN) and have lost HLA-A\*02 expression. The main questions this study aims to answer are: Phase 1: What is the recommended dose that is safe for patients Phase 2: Does the recommended dose kill solid tumor cells and protect the patient's healthy cells Participants will be required to perform study procedures and assessments, and will also receive the following study treatments: Enrollment and Apheresis in BASECAMP-1 (NCT04981119) Preconditioning Lymphodepletion (PCLD) Regimen Tmod CAR T cells at the assigned dose

This study investigates if circulating tumor DNA (ctDNA) and other tumor-related molecules/chemicals released in the blood can help doctors predict if colorectal cancer may come back or spread. Tumors shed DNA and other cancer related chemicals into the blood that can be identified and studied further to provide information about the cancer. Information gathered from this study may help researchers better understand if ctDNA found in the blood can predict whether colorectal cancer may come back or spread.

This is a first-in-human, open-label, non-randomized, three-part phase 1 trial of INBRX-109, which is a recombinant humanized tetravalent antibody targeting the human death receptor 5 (DR5).

This phase II trial tests the effect of the botensilimab in combination with balstilimab in treating patients with stage II/III colorectal adenocarcinoma with detectable circulating tumor (ct) deoxyribonucleic acid (DNA) in the blood. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving botensilimab and balstilimab may be an effective combination to remove any remaining microscopic cancer cells in the bloodstream in patients with stage II/III colorectal adenocarcinoma. In addition, clearing the ctDNA from the blood may serve as an early indicator of treatment response.

Colorectal cancer is the third most common cancer in men, and the second most common in women. Screening for colorectal cancer is based on the search for blood in the stool using fecal immunochemical test (FIT). Occult bleeding is an indication for colonoscopy. In a FIT positive population, 60% of colonoscopies are negative, 34% diagnose an adenomatous lesion, and 6% a cancer. The identification of new biological markers could reduce the number of colonoscopies performed. Cancer cells release extracellular vesicles that contain proteins, mRNAs, DNA, which they can transfer to neighbouring or distant cells. The use of exosomal proteins as novel tumor markers looks very promising. We performed a pilot study comparing the levels of different exosomal proteins in 74 subjects which was recently accepted for publication in Journal of Clinical Laboratory Analysis. Comparison of results showed that only matrix metalloproteinase 14 (MMP14) was significantly higher in patients with colorectal cancer or adenoma than in people with normal colonoscopy. The primary objective of the current study is to determine the best cut-off value of MMP-14 for colorectal cancer screening and to evaluate the performance (Sensitivity, Specificity…) associated to this cut-off value. The secondary objective will be to determine the best cut-off value of MMP-14 for colorectal adenomas screening and to evaluate its performance. For this purpose, 650 patients, seen for diagnostic colonoscopy following a positive FIT test, will be included in the study. After blood collection and exosome isolation, MMP-14 will be measured using a quantitative test (enzyme-linked immunosorbent assay) and the results will be associated with colonoscopy results to determine the sensitivity, specificity, positive predictive value (PPV) and net present value (NPV).

This trial is a Phase III study. The purpose of this study is to evaluate the efficacy and safety of AK112 and chemotherapy versus bevacizumab and chemotherapy for the first-line treatment of metastatic colorectal cancer.

The aim of this study is to evaluate the activity of first-line trastuzumab-deruxtecan, capecitabine and bevacizumab in terms of overall response rate for patients with HER-2 positive metastatic/locally advanced unresectable colorectal cancer

Low-residue diet (LRD) in patient improves the quality of the colon cleanliness and thus the adenoma detection rate (ADR). This is a key criterion in colonoscopy screening for colorectal cancer (CRC). The benefit of an LRD lasting more than 24 hours before colonoscopy has not been demonstrated compared to a 24-hour LRD. Few studies have evaluated the benefit of a prepackaged 24-hour LRD compared to simply receiving oral and written LRD instructions during a consultation. The aim of the study is to evaluate the usefulness of a prepackaged LRD (Colobox®) compared to simple LRD instructions on colon cleanliness (Boston score) in patients examined by endoscopy.

Phase 1 dose escalation and expansion study of CLSP-1025, a first-in-class HLA-A\*02:01 specific T cell engager (TCE) targeting solid tumors that harbor the p53 R175H mutation.

Approximately two-thirds of all colorectal cancer patients undergo surgery with the aim of curing them. However, despite the surgery, 20-25% of them experience relapse. It is possible to reduce the risk of relapse with chemotherapy, but as chemotherapy is associated with significant side effects, it is only given to patients at high risk of relapse. Currently, the risk is assessed based on an examination of the removed tumor tissue. In a previous research project, blood samples were taken after patients' surgery and examined for the presence of circulating tumor DNA (ctDNA). When cancer cells in solid tumors die, they release DNA, which can be detected in the blood. DNA in the blood has a half-life of less than 2 hours, so if ctDNA is found in a blood sample taken, e.g., 14 days after surgery, the patient most likely still has cancer cells in their body. The results show that if a patient has ctDNA in their blood after surgery, the risk of relapse is high. The presence of ctDNA in the blood has the potential to be a better indicator of the risk of future relapse than the tumor examination used today. Therefore, ctDNA analysis has the potential to become a marker that will be used in the future clinical setting for monitoring colorectal cancer. The overall objective of this study is to confirm that ctDNA found in a blood sample after intended curative treatment for CRC is a marker of residual disease and risk of recurrence and is applicable in clinical practice.

The study involves the planned use of a new microwave-based device during colonoscopy procedures in 50 patients to assess the performance and safety of its use for detection of colorectal polyps and lack of normal clinical practice modification. The device is a final design version, which has been previously tested in several preclinical studies (including phantom studies, an ex vivo study with human tissues, and an in vivo study with porcine model) and in a pilot study in humans (NCT05477836)

The goal of this study is to test A2B395, an allogeneic logic-gated Tmod™ CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), renal cell carcinoma (RCC) and other solid tumors that express EGFR and have lost HLA-A\*02 expression. The main questions this study aims to answer are: * Phase 1: What is the recommended dose of A2B395 that is safe for patients * Phase 2: Does the recommended dose of A2B395 kill the solid tumor cells and protect the patient's healthy cells Participants will be required to perform study procedures and assessments, and will also receive the following study treatments: * Enrollment in BASECAMP-1 (NCT04981119) * Preconditioning lymphodepletion (PCLD) regimen * A2B395 Tmod CAR T cells at the assigned dose

This is an open, multicenter phase Ib/II clinical study. The goal of this study is to confirm the Phase II recommended dose (RP2D) of AK129 combinations for advanced solid tumors and evaluate the safety and efficacy of AK129 combinations for non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), colorectal adenocarcinoma (CRC), and other advanced solid tumors.

Colorectal cancer (CRC) is among the most prevalent cancers globally, with approximately one to two million new cases diagnosed each year. This makes CRC the third most common cancer and the fourth leading cause of cancer-related deaths, with 700,000 deaths per year, exceeded only by lung, liver and stomach cancers. CRC accounts for about 10% of all cancer diagnoses worldwide (Sung et al., 2021; Masetti et al., 2022) . CRC affects different races and ethnicities at various age groups in distinct ways. Among patients younger than 50 years old, the proportion of CRC is nearly double for Black individuals (16%) compared to White individuals (9%) and Hispanic individuals (6%). In Egypt, CRC ranked the seventh among cancers, following lung, breast, prostate, liver, and bladder cancers (Mounir et al., 2022). Tumor budding (TB) is characterized by the presence of individual tumor cells or small clusters of up to four cells at the invasive margin of a tumor. This histological feature, which indicates the separation of malignant cells from the main tumor mass, has intrigued pathologists since it was first identified in the 1950s (Giordano et al., 2024). Evaluating TB is crucial for improving prognostic accuracy and informing treatment decisions. Tumors with high-grade TB exhibit a significantly lower 5-year Disease-Free Survival (DFS) rate compared to those with low-grade TB. High-grade TB is regarded as a negative prognostic factor and is associated with an increased risk of recurrence (Kyong Shin et al., 2023). TB can be observed in conventional slides when prominent, but careful observation is necessary. A more thorough assessment of TB is more easily achieved if the neoplastic epithelium is highlighted using pan-cytokeratin immunostains (Mishra et al., 2022). Pan-keratin (Pan-CK) antibodies are proteins derived from cytoskeletal intermediate filaments. These antibodies are a mixture designed to detect multiple low and high molecular weight keratins. Their primary purpose is to allow for the immunohistochemical identification of all epithelial cell types, regardless of their tissue of origin, using a single diagnostic tool. In surgical pathology, Pan-CK antibodies are commonly used to confirm the epithelial origin of both neoplastic (tumorous) and non-neoplastic tissues, as well as to identify small metastases in lymph nodes. However, there are limitations to the assumption that Pan-CK antibodies will stain all epithelial tumors and that non-epithelial tissues will be "keratin negative." It has been reported that a diverse range of epithelial tumors can be Pan-CK negative, challenging the notion that these antibodies are universally applicable (Wick et al., 1986; Badzio, 2019). Pan-CK can help diagnose disease like breast cancer, lung cancer, prostate cancer, and colorectal cancer. It is often used in conjunction with other antibodies for these specific cancers (Chu and Weiss, 2002).