Rectal Cancer

This clinical trial studies whether an exercise program can be successfully delivered to patients receiving treatment for cancer through virtual sessions and allow patients to exercise in their own home. Treatments for cancer can cause side effects such as fatigue and loss of strength. These side effects can make it difficult to work, take care of family, and do other things the patient wants to do. Preliminary research shows that exercise can help prevent some of these side effects, but it can be more difficult to start an exercise program when a patient is receiving cancer treatment. The exercise program in this study is delivered through telehealth (TH) video calls. The TH sessions are delivered by trained staff that supervise resistance exercises. The trained staff also provide guidance to the patient on completing unsupervised aerobic sessions on their own. This may be a successful way to deliver an exercise program and make it easier for cancer patients to exercise in their own home during treatment.

This prospective observational, non-therapeutic study for patients with T3, T4, or node positive rectal cancer eligible to undergo total neoadjuvant therapy. This research study involves the collection of data and biospecimens (blood and tissue) to see if the presence of circulating tumor DNA (genetic material) ctDNA will help monitor rectal cancer more closely and potentially detect a recurrence before routine scans, performed per standard of care C2i Genomics, a biotechnology company, and the Spier Foundation are supporting this research study by providing funding for the study.

This is phase 2 trial of neoadjuvant therapy and short-course radiotherapy in resectable rectal cancer.

The iCaRe2 is a multi-institutional resource created and maintained by the Fred \& Pamela Buffett Cancer Center to collect and manage standardized, multi-dimensional, longitudinal data and biospecimens on consented adult cancer patients, high-risk individuals, and normal controls. The distinct characteristic of the iCaRe2 is its geographical coverage, with a significant percentage of small and rural hospitals and cancer centers. The iCaRe2 advances comprehensive studies of risk factors of cancer development and progression and enables the design of novel strategies for prevention, screening, early detection and personalized treatment of cancer. Centers with expertise in cancer epidemiology, genetics, biology, early detection, and patient care can collaborate by using the iCaRe2 as a platform for cohort and population studies.

A Single-Center, Single-Arm Study of Neoadjuvant Short-Course Radiotherapy Followed by Sequential Immunotherapy with CAPOX Combined with PD-1 antibody and IL-2 for Locally Advanced Rectal Cancer

The goal of this clinical trial is to learn if close follow-up alone (active surveillance) works as well as radiation combined with chemotherapy (chemoradiotherapy) after removing early rectal cancer in adults. The main questions it aims to answer are: 1. Does active surveillance cause fewer serious adverse events than chemoradiotherapy within 3 years? Serious adverse events include a permanent or temporary ostomy (a surgical opening in the belly to pass stool), major bowel problems, or severe treatment-related complications. 2. Is active surveillance as safe as chemoradiotherapy in preventing cancer from coming back or spreading within 3 years? Researchers will compare active surveillance to chemoradiotherapy to see if surveillance causes fewer serious adverse events while keeping cancer outcomes comparable. To join this study, participants must be adults who had an early-stage rectal cancer (T1) removed by an endoscopic procedure, and whose removed tumor showed certain features that raise the risk of cancer cells remaining nearby. Participants will be randomly placed in one of two groups: 1. Active surveillance group: Participants will have regular checkups, blood tests, flexible camera exams of the bowel (rectoscopy), scans of the pelvis and abdomen, and colonoscopy on a set schedule for 5 years. If cancer comes back, doctors will propose further treatment options. 2. Chemoradiotherapy group: Participants will receive radiation to the pelvis along with a chemotherapy pill (capecitabine) or an intravenous (IV) chemotherapy drug (5-FU) for about 5 weeks. After treatment, they will have regular checkups and scans for 5 years.

With 50 patients included, this trial would be the largest pilot study evaluating the value of MRI PET in locally advanced rectal cancer. On the other hand, it would be the only pilot study performing several MRI PET during neoadjuvant treatment. Presumably, the response assessed at the 2nd MRI PET (before cycle 4 or induction chemotherapy) would be predictive of the overall response at the end of neoadjuvant treatment. Then, it would be possible to predict precociously the tumor response.

The goal of this clinical trial is to learn whether using a reinforcing material called SIS (small intestinal submucosa) during bowel connection after rectal cancer surgery can help prevent anastomotic leakage-a serious complication where the connection between two parts of the intestine fails to heal properly. This study will focus on patients with mid-to-low rectal cancer who are scheduled for surgery. The main questions the study aims to answer are: Does using an SIS-reinforced connection reduce the rate of anastomotic leakage within 30 days after surgery compared to standard connection methods? Does it also reduce the need for a temporary stoma (an opening in the abdomen for waste removal)? Researchers will compare two groups: Intervention group: Patients who receive the SIS-reinforced connection during surgery. Control group: Patients who receive the standard connection without reinforcement. Participants in this study will: Be randomly assigned to either the intervention or control group. Undergo standard laparoscopic or robot-assisted rectal cancer surgery. Be followed up at 30 days, 90 days, and 12 months after surgery to check for complications, stoma status, and quality of life. This study is being conducted across multiple hospitals in China to ensure the results are reliable and widely applicable.

This trial (molecular characterization trial) focuses on rectal cancer, a common cancer that is treated with radiotherapy (RT) as standard of care and represents a setting in which to study the effects of RT on the immune system.

This is an open-label multicenter, single-arm Phase II study of Fruquintinib in combination with FOLFIRI (leucovorin calcium (folinic acid), fluorouracil, and irinotecan) in participants with metastatic colorectal cancer (mCRC). The main goals of this study are to: * Evaluate the efficacy of the combination of fruquintinib + FOLFIRI in the 2nd-line mCRC setting * Evaluate the safety of the combination of fruquintinib + FOLFIRI

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 prospective, randomized phase II trial is designed to evaluate whether low-dose short-course radiotherapy differs from common-dose short-course radiotherapy in terms of efficacy when both regimens are sequentially combined with CAPOX, a PD-1 monoclonal antibody, and interleukin-2 (IL-2) in patients with locally advanced rectal cancer. The study is based on findings from our previous single-center, single-arm PRIDE01 study, in which neoadjuvant short-course radiotherapy followed by systemic chemoimmunotherapy and IL-2 demonstrated encouraging antitumor activity relative to historical short-course radiotherapy-based approaches. The current trial aims to provide more robust clinical evidence regarding the potential role of low-dose radiotherapy combined with IL-2 as a sensitization strategy in multimodal neoadjuvant therapy. By comparing complete response rates between the two radiotherapy dose levels, this study may help define an optimized neoadjuvant approach and support future organ-preservation strategies for patients with locally advanced rectal cancer.

This study is being done to answer the following questions: Is the chance of rectal cancer responding the same if chemotherapy alone is given before limited surgery compared to chemotherapy and radiation therapy given together before limited surgery? If radiation therapy is not given, is quality of life better?

The goal of this observational study is to learn about the spatial distribution and significance of metastatic lymph nodes in colorectal cancer patients. The main question it aims to answer is: * What is the spatial distribution pattern of metastatic lymph nodes in patients with colorectal cancer? * Can the spatial distribution pattern of metastatic lymph nodes in patients with colorectal cancer guide clinical practice? Participants should undergo regular follow-up examinations for at least 5 years after the surgery.

SYNCHRONOX is a multicenter cohort (retrospective then prospective) intending to include 550 patients with mid or low rectal adenocarcinoma (pMMR, T3-T4 and/or N+) and resectable synchronous liver metastases, treated upfront with at least two cycles of induction FOLFIRINOX chemotherapy. The primary objective is to determine, at 18 months, the R0 resection rate of both tumor sites (rectum and liver), while secondary objectives focus on 3 year overall and progression free survival, radiological and pathological responses, postoperative morbidity and mortality, and comparison of the different surgical strategies after FOLFIRINOX.

The goal of this clinical trial is to investigate whether adjuvant chemotherapy can prevent disease recurrence in patients with high-risk rectal cancer who have detectable ctDNA after surgery. The main research question the REACT study aims to answer is: \- Does adjuvant chemotherapy improve disease-free survival in patients with high-risk rectal cancer with detectable ctDNA after surgery? Interventions: \- Patients with detectable ctDNA after surgery and randomised to the experimental group will be offered adjuvant chemotherapy (4 cycles CAPOX/6 cycles FOLFOX) within 12 weeks after surgery.

The equilibrium of intestinal microorganisms is essential for health an imbalance has been associated with an increased risk in the development of different pathologies; including colorectal cancer. Rectal cancer is the third most common neoplasm worldwide and the complete excision of the mesorectum is a major prognostic factor. The identification of microorganisms in the adipose tissue that surrounds the small intestine in inflammatory diseases, together with bacterial alterations found in colonic mucosa and feces in patients with rectal cancer in comparison with healthy individuals indicates that microbiome alteration plays an essential role in pathogenesis. The mesorectal microbiome in rectal cancer patients stills unknown and given its importance in the prognostic of the disease the goal of this study is to identify microbial profiles that allow predicting rectal cancer patients with a poor prognosis.

Rectal cancer presents a significant global health challenge. Despite improvements in clinical outcomes, significant disparities persist across Europe. These differences are explained not only by the heterogeneity of risk factors and screening strategies, but also by variations in diagnostic and therapeutic approaches, which are highly dependent on medical imaging. Standard treatment for locally advanced rectal cancer based on staging MRI is neoadjuvant treatment (NAT), for tumour downsizing and downstaging, followed by total mesorectal excision. In a significant proportion of cases, radical surgery leads to substantial long-term complications like sexual and urinary dysfunction, fecal incontinence, and impairment in daily activities. Given that up to 42% of patients show complete tumor regression at pathology (i.e. pathological complete response pCR), to avoid unnecessary radical surgery, non-operative management has become an attractive alternative when there are no signs of viable tumour after NAT (i.e. clinical complete response cCR). Such patients are candidates for Watch-and-Wait (W\&W), an established active surveillance policy in specialized centers worldwide relying on clinical examination, endoscopy and MRI. On the other hand, W\&W carries a risk of local regrowth (persistence of microscopic residual disease despite apparent cCR). Even in expert hands, assessment of tumor response is not perfect and local regrowth based on current selection methods occurs in \~30% of cases. Although deferred surgery is a successful treatment with no apparent negative impact on local disease control, an increased rate of distant metastases has been recently reported. Therefore, there is a critical unmet clinical need to detect complete responses after NAT and avoid unnecessary surgery with its associated morbidity and quality of life impairment risks, while also improving sensitivity for residual microscopic disease that will result in local regrowth and associated reduced disease-free survival. Rectal cancer poses a burden not only on healthcare systems, but also on patient well-being. Patients frequently suffer from feelings of isolation and helplessness when faced with unpredicted disease-related situations, given the common difficulties to access high quality information and communicate with attending physicians. As such, there is a clear need to unburden healthcare facilities from unnecessary hospital visits, while improving patient outcomes, engagement, support and care.

Colorectal cancers and ovarian cancers are respectively the 2nd and 5th cause of cancer mortality in France. Surgical resection is a crucial step in the therapeutic management of colorectal cancers. For advanced ovarian cancers, the objective of cytoreductive surgery is to obtain complete macroscopic resection with no visible residual disease. One or more digestive resections are often required to achieve this goal of complete surgery (usually a modified posterior pelvic exenteration with colorectal resection). A ligation of the inferior mesenteric artery at its origin is classically performed in left colectomies and rectal resection for colorectal cancers. This allows the resection of the colorectal segment with a complete mesocolic lymphadenectomy until the origin of the inferior mesenteric artery and a good mobilization of the descending colon to allow its anastomosis to the underlying rectal stump. This ligation of the inferior mesenteric artery at its origin is also frequently performed in cases of modified posterior pelvic exenteration for ovarian cancer. Recently, several studies suggest that arterial ligation of the inferior mesenteric artery could be performed below the emergence of the left colic artery. Its preservation requiring a meticulous vascular dissection would allow a better vascularization of the descending colon and of the colorectal anastomosis without affecting the carcinologic quality of the resection and the number of resected lymph-nodes. Indeed, the most feared complication during colorectal anastomosis is the anastomotic leakage whose rates are on average 15% in rectal cancer with low anastomosis and 6% in ovarian cancers. Verifying the adequate vascularization of the descending colon before performing the colorectal anastomosis is a crucial step in reducing the risk of postoperative fistula. However, quantifying this vascularization is challenging, and several techniques can be used to assess it. The gold standard technique involves measuring arterial pressure using a catheter inserted into the marginal artery of the descending colon. Other non-invasive techniques also use Doppler studies to calculate pressure in the marginal artery or assess oxygen saturation using a sterile sensor. Studies have shown that the use of indocyanine green in colorectal surgery, particularly to evaluate perfusion before the creation of an anastomosis, significantly reduces the rate of anastomotic leakage. Indocyanine green is a fluorescent dye that, after intravenous injection, binds to plasma proteins and allows tissue perfusion to be visualized using a fluorescence system. The objective of this project is to show that the preservation of the left colic artery is possible and allows a better vascularization of the descending colon before colorectal anastomosis.

The purpose of the study is to learn more about how the body responds to standard treatment (chemoradiation and chemotherapy). The study will use the results of testing down on participants' blook, tissue, and scans to learn more about how people with rectal cancer respond to chemoradiation and chemotherapy treatment and if it is useful for predicting whether a person's cancer get better, gets worse, or stats the same after treatment.

The goal of this prospective study is to evaluate if a higher radiation dose to the tumor can increase the organ preservation rate in non-locally advanced rectal cancer.

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.

Background: A new cancer therapy involves taking white blood cells from a person, growing them in the lab, genetically modifying them, then giving them back to the person. This therapy is called gene transfer using anti-KRAS G12V mTCR cells. Objective: To see if anti-KRAS G12 V mTCR cells are safe and can shrink tumors. Eligibility: Adults at least 18 years old with cancer that has the KRAS G12V molecule on the surface of tumors. Design: In another protocol, participants will: Be screened Have cells harvested and grown Have leukapheresis In this protocol, participants will have the procedures below. Participants will be admitted to the hospital. Over 5 days, participants will get 2 chemotherapy medicines as an infusion via catheter in the upper chest. A few days later, participants will get the anti-KRAS G12V mTCR cells via catheter. For up to 3 days, participants will get a drug to make the cells active. A day after getting the cells, participants will get a drug to increase their white blood cell count. This will be a shot or injection under the skin. Participants will recover in the hospital for 1-2 weeks. They will have lab and blood tests. Participants will take an antibiotic for at least 6 months. Participants will have visits every few months for 2 years, and then as determined by their doctor. Visits will be 1-2 days. They will include lab tests, imaging studies, and physical exam. Some visits may include leukapheresis or blood drawn. Participants will have blood collected over several years.

This phase II clinical trial is evaluating whether adding KRC-01 injections to standard chemoradiotherapy may improve treatment outcomes in patients with locally advanced rectal cancer without metastases. KRC-01 is an investigational product designed to improve the effectiveness of radiotherapy by increasing oxygen levels inside tumors, which may help radiation work better. KRC-01 contains hydrogen peroxide and sodium hyaluronate and is injected directly into the tumor before radiotherapy sessions. Previous clinical experience in Japan, including studies in several types of cancer, suggested that this approach may improve tumor oxygenation and enhance the effect of radiotherapy. The main objective of the K-BOOST study is to evaluate how many patients achieve a complete clinical response after treatment with chemoradiotherapy combined with intratumoral KRC-01 injections, potentially allowing some patients to avoid surgery. Surgery may still be recommended depending on the individual response to treatment. Approximately 24 patients will participate in this multicenter French study. The experimental treatment period lasts approximately 26 weeks, and participants will be followed for up to 2 years.

The goal of this clinical trial is to learn if somatostatin plus a clear liquid diet can help prevent severe leakage after rectal cancer surgery in adults with low or mid rectal cancer who are scheduled to have ultra-low anterior resection. These patients have a higher risk of leakage where the bowel is joined together after surgery. The main questions it aims to answer are: Does somatostatin plus a clear liquid diet prevent severe leakage within 1 month after surgery about as well as a prophylactic diverting stoma? What medical problems, bowel function problems, recovery outcomes, and quality of life outcomes do participants have after surgery and during follow-up? Researchers will compare somatostatin plus a clear liquid diet without a diverting stoma to prophylactic diverting stoma to see if the somatostatin plus clear liquid diet regimen can provide similar protection against severe leakage while reducing the need for stoma creation. Participants will: Have rectal cancer surgery with the bowel joined very close to the anus Be randomly assigned to receive either somatostatin plus a clear liquid diet for 7 days after surgery without a diverting stoma, or a prophylactic diverting stoma Have follow-up assessments of leakage, postoperative complications, bowel function, recovery quality, and quality of life Complete follow-up visits or assessments for up to 3 years after surgery