Colon Cancer

Background: Genes are the instructions a person s body uses to function. Genome sequencing reads through all of a person s genes. Everyone has many gene variants, and most do not cause disease. Some gene variants called secondary findings may be important for a person s health even if they are not related to the reason why a person had genome sequencing done. Researchers want to learn more about what it means to have a secondary finding. Objectives: To learn about how gene variants may affect a person s health. To learn about how people understand their genetic test results. Eligibility: People with secondary findings from genetic testing done as part of a research study, clinical care, or other methods. Design: Participants may be asked to do an online survey and phone interview to ask what they think about their results, their healthcare, and if they talk with their family about the result. Eligible participants may be offered a visit to the NIH Clinical Center where they will be evaluated for health problems related to the secondary finding. DNA samples that were already collected may be studied. Participants may be asked to send in a second DNA sample (blood or saliva). These will be used to verify any findings. Participants who have a secondary finding can get genetic counseling.

This interventional cohort study will evaluate circulating tumor DNA (ctDNA) and tumor-educated platelets (TEP) as blood-based biomarkers in adults with stage III colon cancer who are planned to receive neoadjuvant systemic therapy followed by surgical resection. Treatment will be given according to routine clinical practice and will depend on the biological characteristics of the tumor, including mismatch repair status. Participants will provide additional blood samples at predefined time points before, during, and after treatment and surgery. These samples will be used to analyze ctDNA and TEP and to assess whether changes in these biomarkers are associated with radiological response, pathological response, and disease-free outcomes. Approximately 80 participants will be enrolled at the Institute of Oncology Ljubljana. Participants will not receive experimental drugs as part of this study.

Cancers of the upper aerodigestive tract account for around 4% of all malignant tumours worldwide. Colon and liver cancer are the most common digestive cancers. The epidemiology of liver cancer is changing, and the number of deaths from liver cancer has increased by 25% worldwide. In France, around 19,000 cancers of the upper aerodigestive tract and 88,000 new cases of digestive cancer are diagnosed each year (colon cancer remains the most common). Patients with these two types of cancer are at particularly high risk of undernutrition. In cancer patients, changes in diet may result from constraints linked to the cancer or possible after-effects, but also from personal choices (for example, adopting a healthier diet). Cancer and its treatment lead to changes such as increased nutritional requirements and hypercatabolism, or sensory changes (taste and smell), reducing pleasure and food intake. These problems will impair quality of life and intensify undernutrition, a major problem in the management of the disease since it increases the risk of complications, therapeutic failure and mortality. It is estimated that 10-20% of deaths in cancer patients are attributable to the consequences of undernutrition rather than to the disease itself. In the VICAN study, 41% of patients changed their diet after diagnosis: 29% because of changes in taste and 82% to have a healthier diet. These changes were associated with the treatment received, the presence of sequelae and anxiety. Taste and smell disorders are common in different types of cancer (any solid or haematological type) and treatments (chemotherapy, radiotherapy and surgery. The mechanisms involved in sensory changes are not fully understood, especially in cancer, and with different types and treatments. Several hypotheses have been proposed: altered expression of enzymes of the oral sphere, altered expression of sensory receptors, saliva composition and function, and impact of the oral microbiota. The early identification of undesirable effects linked to nutrition, and the early or anticipated diagnosis of undernutrition are important issues in the management of cancer patients. The pleasure (or displeasure) produced by food guides desire and eating behaviour. The mechanisms involved are linked to hedonic sensations: conditioned satiety, specific sensory satiety, negative alliesthesia and the reward system (hedonic system). The latter is influenced by the environment and can be consciously controlled, with several dimensions: liking (the patient likes or dislikes a given food) and wanting (evaluates the desire to consume a given food at a given moment). All these parameters, together with sensory and dietary learning throughout life (habits, beliefs and constraints), influence food preferences and therefore eating behaviour. Individual sensitivities and the personal history of the disease (treatment and care pathway, sequelae, presence of co-morbidities, etc.) must therefore be taken into account when setting up preventive actions for cancer patients. It seems important to explore these factors, the experience of patients and the consequences for eating behaviour in daily life, in order to improve support and communication with healthcare professionals, as well as prevention and early detection of undernutrition. It would be interesting to conduct more in-depth studies on nutritional status, quality of life and changes in taste and smell, which in most studies have been considered separately.

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 first-in-human study will evaluate safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of PHN-012, a novel antibody-drug conjugate (ADC), in patients with advanced solid tumors.

PRE-ISPY Phase I/II (I-SPY-P1) is an open-label, multisite platform study with multiple ongoing drug regimen arms added by protocol amendment which is designed to evaluate single agents or combinations in locally advanced, incurable, or metastatic solid tumors and/or oligometastatic malignancy and/or a high risk of recurrence following prior treatment with curative intent. The overall goal is moving promising drug regimens into a larger phase II (or III) trial and in general could feed the neoadjuvant breast I-SPY 2 Trial (NCT01042379) and/or other oncology solid tumor trial in a timely manner.

This study will collect blood from patients with cancer to study the level of cells which decrease the immune response (suppressor cells) before and after chemotherapy. Patients 18 years of age and older with cancer may participate. This study does not involve treatment. Participants will have about 50 ml (3 tablespoonfuls) of blood drawn. Depending on their condition, patients may be invited to enroll in a clinical research study involving chemotherapy, radiotherapy, or surgery. Additional 40-ml blood samples may be drawn during the course of treatment. ...

This prospective, multicenter, single-arm phase II interventional study evaluates whether longitudinal circulating tumor DNA (ctDNA) monitoring can guide neoadjuvant immunotherapy and surgical decision-making in dMMR/MSI-H colon cancer. Participants with ctDNA clearance proceed to curative surgery, whereas those with persistent ctDNA positivity escalate to combined PD-1 and CTLA-4 inhibitor therapy.

The objective of this protocol is to develop an institution-wide liquid biopsy protocol that will establish a common process for collecting blood and corresponding archived tumor specimens for future research studies at the University Health Network's Princess Margaret Cancer Centre. Circulating cell-free nucleic acids (cfNA), including cell-free DNA (cfDNA) and cell-free RNA (cfRNA), are non-invasive, real-time biomarkers that can provide diagnostic and prognostic information before cancer diagnosis, during cancer treatment, and at disease progression. Cancer research scientists and clinicians at the Princess Margaret are interested in incorporating the collection of peripheral blood samples ("liquid biopsies") into research protocols as a means of non-invasively assessing tumor progression and response to treatment at multiple time points during a patient's course of disease.

This multicenter, randomized, open-label, blinded-endpoint Phase II trial assesses the efficacy and safety of tolecizumab (PCSK9 inhibitor) plus sintilimab/CapeOX chemoimmunotherapy as neoadjuvant treatment for pMMR/MSS locally advanced colon adenocarcinoma .

This is a Phase 1, first-in-human (FIH), open-label, multicenter study designed to evaluate the safety, tolerability, PK, and preliminary anti-tumor activity of SHY-ONC6 in participants with advanced or metastatic solid tumors who have progressed on or are intolerant to standard therapies. The study will consist of 2 parts: a dose escalation part (Phase 1a) and a dose expansion part (Phase 1b).

This research study is being conducted to improve the quality of care of participants who have a diagnosis of gastrointestinal cancer (anal, colon, rectal, esophageal, stomach, small bowel, appendix, pancreas, gall bladder, liver, neuroendocrine tumor of gastrointestinal origin). This study has 3 components as follows- 1. Ensuring appropriate biomarker testing and evidence-based care: Biomarkers are molecules in the tumor or blood that indicate normal or abnormal processes in participant's body and may indicate an underlying condition or disease. Various molecules, such as DNA (genes), proteins, or hormones, can serve as biomarkers since they all indicate something about participant's health. Biomarker testing can also help choose participant's treatment. Additionally, a tumor board will be conducted periodically to provide treatment recommendations to participant's treating physician. Participants will receive standard-of-care treatment if participant enroll in this study. Participant will not receive any experimental treatment. 2. Assistance with clinical trial enrollment. The study team will help participants enroll in a clinical trial appropriate for participant's condition. However, enrolling in a clinical trial is totally up to the participant. 3. Health literacy: The study team will provide information relevant to participant's diagnosis to enrich participant's understanding of participant's condition and treatment. Investigator will provide questionnaires to assess participant's understanding before and after participant's have been provided with educational/informational material appropriate for participant's diagnosis.

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 this multi-phase research study is to understand how consultation of cancer care with a geriatrician can best improve outcomes for older adults with gastrointestinal malignancies.

The goal of this clinical trial is to learn if giving two medicines together, porustobart and pembrolizumab, before surgery can treat a common type of colon cancer called microsatellite stable (MSS) colon cancer in adults. This type of cancer can be removed with surgery and has not spread to other parts of the body. Both medicines work by helping the immune system fight cancer. The main questions this study wants to answer: How well do the medicines destroy the cancer before surgery? What side effects do participants have when taking the medicines? Researchers will compare two groups to see which treatment schedule works better and is safer. Both groups get pembrolizumab. One group gets one dose of porustobart (Day 1 only), and the other group gets two doses (Day 1 and Day 22). Participants will: Complete certain tests and procedures to make sure they are eligible Get the medicines through a vein on Day 1 and Day 22 then have surgery 6-9 weeks after starting treatment Return for checkups and tests every 6 months for up to 3 years after surgery

This is a first-in-human Phase 1 study of DEM301 in adults with previously treated advanced metastatic colorectal cancer. DEM301 is an investigational antibody-drug conjugate. The study will evaluate the safety and tolerability of DEM301, identify doses for further study, and assess how the drug behaves in the body and whether it shows signs of activity against the cancer.

The incidence of cancer among older adults is increasing as a result of longer life expectancy. Therapeutic advances have led oncologists to propose new available treatments for these patients, particularly oral therapies, whether targeted therapies or hormone therapies. However, these patients are more vulnerable and have an increased risk of treatment-related toxicity or inefficacy. Indeed, they more frequently suffer from comorbidities (renal, cardiac, hepatic insufficiency, etc.) and present risk factors (polypharmacy, cognitive disorders, etc.) known to reduce the effectiveness or increase the toxicity of oral therapies due to variations in plasma drug concentrations. For several years, various international recommendations (ASCO, ESMO, etc.) have suggested that specialized geriatatric oncology care is indicated for these patients. Similarly, some studies have shown that pharmacist involvement may have an impact by reducing drug-drug interaction issues or non-adherence. Finally, the introduction of oral therapies in oncology has raised pharmacological challenges: regular pharmacokinetic monitoring could allow dose adjustments in cases of disease progression in undertreated patients or toxicity in overexposed patients. Our hypothesis is that implementing an integrative care pathway in this population could demonstrate a benefit by improving quality of care, reducing toxicity, optimizing efficacy, and maintaining an acceptable cost. This approach could help prevent early treatment discontinuation due to disease progression related to insufficient drug concentrations, as well as certain toxicities related to overdosing (e.g., drug-drug interactions), leading to improved quality of life and a reduction in rehospitalization rates.

Female patients with early onset (\<50 years old) pelvic malignancies such as uterine and rectal cancers are rising in incidence, which often requires pelvic radiation; many of these patients are premenopausal and at a high risk of premature ovarian failure from radiotherapy. Premature ovarian failure carries significant cardiac, musculoskeletal, sexual, and psychosocial morbidity. Ovarian transposition carries variable success rates, is not readily accessible to the general population, and can still be at risk of clinically significant radiotherapy doses. There is an unmet need for innovative techniques to protect ovarian function.

This is a research study to test whether two immunotherapy drugs-cemiplimab and fianlimab-can safely and effectively shrink colon tumors before surgery in people with stage II-III colon cancer that has not spread to other parts of the body. Participants will receive two doses of the study drugs through an IV (one on Day 1 and one on Day 22). During the study, participants will have regular visits to the study clinic and multiple tests for safety and research purposes, including blood tests, along with other tests and scans, followed by surgery to remove the tumor. The study will follow participants' health for up to three years after surgery. Risks of cemiplimab and fianlimab include fatigue, diarrhea, skin rash, thyroid problems, and immune-related side effects such as inflammation of the lungs, liver, or intestines.

This study will investigate the safety, tolerability, pharmacokinetics, and anti-tumor activity of CBI-1214 in participants with advanced or metastatic Microsatellite Stable (MSS)/Microsatellite Instability Low (MSI-L) Colorectal Cancer

Patients with gastric or colon cancer with peritoneal carcinomatosis will receive a biopsy of the tumor during their primary curative surgery. The operation is performed according to standard and includes resection of the primary tumor and any metastases and followed by HIPEC (Intraperitoneal hyperthermic chemoperfusion) according to the respective hospital standard. Organoid cultures from the biopsies are established in the research laboratory. Various chemotherapeutic agents are tested on these tumor organoids in the laboratory and the tumor organoids are analyzed in detail with regard to genetic alterations in order to find alterations that can be addressed, if necessary, by means of targeted drugs against peritoneal carcinomatosis.

The goal of this clinical trial is to evaluate whether Nuvastatic can reduce cancer-related fatigue in adult patients with colon cancer undergoing first-line chemotherapy. The main questions it aims to answer are: Does Nuvastatic significantly reduce cancer-related fatigue compared to placebo? Is Nuvastatic safe and well tolerated in this patient population? Researchers will compare Nuvastatic vs placebo to see if Nuvastatic improves fatigue scores and maintains an acceptable safety profile. Participants will: Receive Nuvastatic or placebo sachets (3 times per day) for 3 cycles of 20 days each (total \~60 treatment days). Continue their standard first-line chemotherapy regimen. Provide blood samples for biomarkers (CEA, CA-125) at Screening and End of Treatment. Complete patient diaries and fatigue assessments as per protocol.

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 is a mixed-methods implementation pilot combining an educational intervention with a mailed stool-based testing outreach feasibility study within a resident primary care clinic. Participants will be assigned by clinic team to education, mailed FIT, mailed Cologuard, or usual care comparison groups.

The efficiency of the D3 lymph node dissection is still controversial for left colon cancer patients. This study will try find difference in 5-year overall survival between D2 and D3 lymph node dissection. Investigation of the functional and short-term outcomes will clarify safety of the D3 lymph node dissection.