Clinical Research Directory

Phase 2 Single-Arm Rectal Cancer Brachytherapy for Patients With Low-Lying Residual Adenocarcinoma After Total Neoadjuvant Therapy to Improve Organ Preservation Rates

Rectal cancer patients who do not achieve a complete response to standard of care chemotherapy and radiation often require surgical resection as part of curative intent therapy. This study will evaluate whether additional "focal" radiation delivered internally (rectal brachytherapy) can provide complete responses and thus spare the requirement for surgery. The main questions are whether: 1) rectal brachytherapy is safe in this clinical treatment paradigm and if 2) rectal brachytherapy improves organ preservation (no need for surgery). The trial involves an additional MRI pelvis and sigmoidoscopy with marker placement to define high-risk residual disease for radiation planning. Subsequently, 3 outpatient brachytherapy treatments are given on a weekly basis. If a patient achieves a complete response to brachytherapy, standard of care non-operative surveillance visits are conducted with study visits aligned during the first two years following brachytherapy.

Evaluation of Quality of Life and Utilities Following Surgical Treatment of Stage I-IV Rectal Cancer

This study evaluates quality of life and utilities following surgical treatment of stage I-IV rectal cancer. This study may help researches learn more about quality of life in patients who have or have had rectal cancer.

A Clinical Study of Calderasib (MK-1084) With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)

Researchers are looking for other ways to treat locally advanced or metastatic colorectal cancer (mCRC) that is unresectable and has a gene mutation called KRAS G12C. Standard (or usual) treatments for this type of colorectal cancer may include mFOLFOX6 with or without bevacizumab. Researchers want to learn if adding calderasib (the study medicine) and cetuximab to mFOLFOX6 can treat locally advanced or mCRC with the KRAS G12C mutation. Calderasib and cetuximab are targeted therapies. The goals of this study are to learn: * About the safety of calderasib with cetuximab and mFOLFOX6 and if people tolerate the treatments * If people who receive calderasib with cetuximab and mFOLFOX6 live longer without mCRC growing or spreading compared to people who receive mFOLFOX6 with or without bevacizumab.

Adaptive Radiation for Locally Advanced Rectal Adenocarcinoma

The purpose of the study is to determine the feasibility of using magnetic resonance imaging (MRI)-guided adaptive chemoradiation therapy to improve response to treatment.

Study of Cabozantinib and Nivolumab in Refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer

Data from a prior phase II study of single agent cabozantinib in metastatic, refractory colorectal cancer (NCT03542877) combined with the compelling preclinical data in colorectal mouse models utilizing cabozantinib combined with nivolumab have led to this concept for a clinical trial to combine cabozantinib and nivolumab in patients with metastatic MSS CRC in the third line setting and beyond.

Short Course Radiation Therapy and Combination Chemotherapy for the Treatment of Stage II-III Rectal Cancer

This phase I trial investigates how well short-course radiation therapy followed by combination chemotherapy works in treating patients with stage II-III rectal cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as leucovorin, fluorouracil, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving short-course radiation therapy and combination chemotherapy may reduce the need for surgery and therefore improve quality of life.

MRI-Guided Adaptive Radiation Therapy for Organ Preservation in Rectal Cancer

This study is a prospective, open-label, phase I design.

A Global, Integrated, Personalized, Stage-related, Multimodal Therapeutic Approach for Rectal Adenocarcinoma Based on Organ Sparing and Mininvasivity

A phase II, single-center, non-profit, interventional study on patients affected by rectal adenocarcinoma. Patients will be stratified into three groups based on pre-treatment clinical stage. The study investigates and may propose a comprehensive, stage-specific, multimodal approach to rectal adenocarcinoma, with a focus on organ preservation even in early stages (cT1-2N0). When organ-sparing strategies are not feasible, the approach prioritizes minimally invasive techniques (laparoscopic and robotic) to reduce the physical, psychological, and quality-of-life impact on patients.

A Study of Tucatinib and Trastuzumab in People With Rectal Cancer

The study researchers believe that a combination of the drugs trastuzumab and tucatinib, given with standard chemotherapy (capecitabine and oxaliplatin/FOLFOX), may help participants with rectal cancer.

Advanced Endoscopic Resections for Rectal Neoplasms

This study evaluates how advanced endoscopic resection techniques affect treatment outcomes in adults with rectal cancer. Rectal cancer has traditionally been treated with standard abdominal surgery. Newer endoscopic techniques allow removal of selected early tumors and may reduce treatment-related complications. However, their effectiveness and safety in tumors with deeper invasion are not yet fully established. This multicenter retrospective observational study uses existing medical records from adults who underwent endoscopic or surgical resection of rectal tumors between 2015 and 2025. Researchers will analyze anonymized information on procedures performed and treatment outcomes to assess the safety and effectiveness of advanced endoscopic approaches. The results of this study may help guide treatment selection and improve care for people with rectal cancer.

Upfront Trastuzumab-Deruxtecan Plus Capecitabine and Bevacizumab for Patients With HER-2 Positive 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

Use of a Novel Camera to Check the Bowel After Polyp or Tumour Removal

1.1 Polyps or tumours in the lower part of the bowel (rectum) can be removed using instruments inserted through the bottom which avoids major surgery and the possibility of a stoma bag (colostomy). Afterwards, it is important to check the area with regular camera tests. If checks are delayed, re-growths could be serious and may be untreatable. COVID and other factors have led to long waiting lists for camera checks and in NHS Lothian around 20% of all camera checks are done more than 6 months late. The investigators want to try a new camera and approach that would allow us to reduce waiting lists. Using a short camera called a 'rectoscope' to check the lower bowel has already been shown to be safe, comfortable and acceptable to patients with other conditions. In fact, patients are unlikely to feel or realise any difference between the rectoscope and standard camera tests. The investigators want to show that this 'rectoscope' can be safely used in the outpatient clinic with an enema (suppository) instead of strong bowel medicine taken by mouth the day before. This would mean the camera checks happen on time and would reduce waiting lists for other important tests. The investigators will include 30 patients across three stages of our study. In the first set of patients, the investigators will use the rectoscope alongside the usual endoscope in the endoscopy room using the usual oral bowel medicine. This stage will check the rectoscope is acceptable to the patient and the doctor. In the next 10 patients the investigators will use a suppository instead of oral bowel medicine still using both cameras. Finally, the investigators will use the rectoscope in the outpatient clinic with an suppository to show this is an easy, effective and acceptable way to deliver timely camera checks.

Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors

The purpose of this study is to find out whether the study drug, TSR-042, followed by standard chemoradiotherapy (the chemotherapy drug capecitabine + radiation therapy) and standard surgery is an effective treatment for advanced dMMR solid tumors. The study will also look at the safety of the study drug.

ctDNA-Informed Management of Early-Stage Rectal Cancer

This is a phase 2 pragmatic study to examine the utility of ctDNA-informed treatment management for participants with early-stage rectal cancer using the Signatera Genome assay. The primary aims are to 1) assess pathologic complete response (path CR) in the ctDNA informed management arm; 2) assess pathologic complete response (path CR) in the post total neoadjuvant therapy (TNT) standard of care (SOC) surgery arm; and 3) assess disease free survival (DFS) in the ctDNA informed management arm.

Reporting of Tumour Deposits in Colorectal Cancer by Radiology and Pathology

Recent research shows that tumour deposits-small spots of cancer found near the main bowel tumour-may give doctors important information about how aggressive the cancer is and how likely it is to come back. Doctors can find tumour deposits either: 1. When looking at scans before surgery, or 2. when examining the removed bowel tissue under the microscope after surgery. In the past, tumour deposits were not always recorded properly. This is because older cancer-staging systems (called TNM 5) used in the UK treated these spots differently, depending on their size, and sometimes labelled them as lymph nodes even when they were not. As a result, many tumour deposits were missed in reports. Since 2018, the UK has been using an updated staging system (called TNM 8) that gives tumour deposits their own category. This means doctors are now expected to report them separately when they are found in the tissue around the bowel. This matters because the investigators know that patients who have tumour deposits may have a higher risk of the cancer returning or spreading. Because of this, these patients might benefit from extra treatment-such as chemotherapy or radiotherapy-on top of surgery. However, if tumour deposits are not routinely recorded on scans or pathology reports, doctors may not realise a patient has them. This means that: 1. Patients may not get the most appropriate advice about their cancer, and 2. Patients may miss out on treatments that could help reduce the chance of the cancer returning. This research project aims to find out two things: 1. Are tumour deposits being routinely reported on scans and pathology reports for rectal cancer since the newer TNM 8 system was introduced? And 2. Is there a link between reporting tumour deposits and another important finding called EMVI (extramural vascular invasion), which also affects cancer behaviour and treatment decisions?

ProLARS Trial: Prospective Longitudinal Follow-up of Low Anterior Resection Syndrome (LARS) and COREFO Score After Rectum Surgery in Patients Undergoing Upfront Surgery or Different Neo-adjuvant Treatment Regimens

OBJECTIVE Low anterior resection syndrome (LARS) is a term for functional bowel complaints occurring after low anterior resection. Symptoms can range from faecal incontinence and frequent loose stools to urgency and incomplete emptying with great impact on quality of life. Little is known about the longitudinal evolution of LARS and the impact of different schedules of neoadjuvant chemoradiotherapy combined with surgery. The investigators aim to investigate the incidence and evolution of functional bowel complaints in function of different neoadjuvant treatment regimens, type of surgery and adjuvant therapy in patients who undergo surgery for rectal cancer. The investigators focus on following objectives: evolution of LARS- and COREFO-scores per treatment regimen and their impact on work incapacity; identification of possible risk factors potentially related to functional outcome; monitoring and treatment of LARS. METHODS This will be a multicentre prospective interventional study. The study population will consist of adult patients with rectal cancer, regardless of any neo-adjuvant therapy. Patients will be included for 5 years with a 2 year postoperative follow-up. Interim analysis will be made after 2 years of inclusion. Patients with intellectual disability or clinical colon obstruction are excluded. Automated online questionnaires including LARS and COREFO scores, incapacity for work and defecation quality will be sent at different time points (figure 1) using REDCap. RESULTS and CONCLUSIONS Longitudinal change of LARS- and COREFO-scores will be visually summarized. Patient, disease or procedure specific risk factors will be assessed as well. LARS is proven to be the principal postoperative problem after rectal surgery. If the investigators can predict the severity of LARS (minor or major LARS), this can be extremely helpful in deciding whether to perform a sphincter-sparing resection or a rectal amputation instead. Furthermore, the investigators want to offer perspective to patients who are susceptible to a disturbed postoperative bowel function.

Active Surveillance and Chemotherapy Before Surgery in Treating Participants With Stage II-III Rectal Cancer

This pilot trial studies how well active surveillance and chemotherapy before surgery work in treating participants with stage II-III rectal cancer. Active surveillance involves monitoring participants for additional tumor growth after receiving cancer treatment. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether deferring surgery after active surveillance and chemotherapy will work better in treating participants with stage II-III rectal cancer.

TAS-102 With Concurrent Radiation for the Treatment of Untreated Resectable Stage II-III Rectal Cancer

This phase 1b trial studies the side effects and best dose of TAS-102 when given together with radiation therapy in treating patients with stage II-III rectal cancer that has not been treated and can be removed by surgery (resectable). Drugs used in chemotherapy, such as TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. This study is being done to find out the safest dose of TAS-102 that can be used with radiation treatment for rectal cancer.

Young-Onset Colorectal Cancer

This study investigates the genetic factors that may influence the risk of developing colorectal cancer at a young age. Finding genetic markers for colorectal may help identify patients who are at risk of colorectal cancer. Studying individuals and families at high risk of cancer may help identify cancer genes and other persons at risk.

Trial Utilizing Metronidazole to Optimize the Microbiome of Rectal Adenocarcinoma Undergoing Neoadjuvant Therapy

To learn if adding metronidazole to standard therapy can decrease populations of Fusobacterium nucleatum (F. nucleatum) and other anaerobes (small organisms that cause infections) in participants with rectal cancer receiving neoadjuvant therapy, compared to neoadjuvant therapy alone.

SCRT Followed by CAPOX + Bev ± PD-1 Inhibitor for TNT in LARC

This study aims to evaluate the efficacy and safety of short-course radiotherapy combined with CAPOX plus bevacizumab with or without a PD-1 inhibitor in patients with locally advanced rectal cancer (LARC). The hypothesis is that the addition of immunotherapy (PD-1 inhibitor) can significantly improve the complete response (CR) rate and enhance local control while reducing the incidence of distant metastasis. This study will compare the effects of sequential chemoradiotherapy and targeted therapy with or without immunotherapy following short-course radiotherapy, aiming to explore the optimal regimen for total neoadjuvant therapy.

Establishing a ctDNA Biomarker to Improve Organ Preserving Strategies in Patients With Rectal Cancer

This study measures the levels of circulating tumor DNA (ctDNA) in patients with stage II-III rectal cancer before, during, and after treatment to find out if the presence or absence of ctDNA in patient's blood using the Signatera test can be used to gauge how different treatments may affect rectal cancer. ctDNA is DNA from the rectal cancer that is circulating in the blood. The purpose of this study is to understand if the way rectal tumors respond to standard treatment can be associated with varying levels of ctDNA.

Family Communications After Genetic Testing

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.

Involve-site Radiotherapy Combined With Chemotherapy and Immunotherapy as Neoadjuvant Treatment for Locally Advanced Rectal Cancer

Surgery is the primary treatment for rectal cancer. However, in patients with locally advanced disease, direct surgery often fails to achieve complete tumor resection. In such cases, neoadjuvant therapy is required to downstage the tumor before surgery. The current standard neoadjuvant approach consists of preoperative radiotherapy and then surgery. Although effective, standard radiotherapy uses large target volumes, which results in significant toxicities, increased surgical complications, and reduced patient compliance and quality of life. In addition, excessive radiation fields can compromise the intensity and timing of systemic therapy, potentially increasing the risk of distant metastasis. This may be one of the key reasons why current neoadjuvant radiotherapy mainly improves local control but has not translated into prolonged overall survival. Emerging evidence suggests that combining immunotherapy with radiotherapy may further enhance treatment efficacy. However, large radiation fields may impair the effectiveness of immunotherapy. Therefore, reducing the radiotherapy target volume may not only decrease treatment-related toxicity but also augment the immunotherapy response. This clinical study is designed to evaluate whether reducing the radiotherapy target volume, when combined with chemotherapy and immunotherapy prior to surgery, can decrease radiotherapy-related toxicities and reduce the risk of distant metastasis, without increasing the local recurrence rate, compared with the current standard radiotherapy fields. The ultimate goal is to improve the efficacy of neoadjuvant therapy in locally advanced rectal cancer while minimizing treatment toxicity, thereby providing new strategies and evidence for preoperative management.