Clinical Research Directory

Multicentric National Italian Analysis of Textbook Outcome in Colorectal Cancer Surgery

Colorectal cancer (CRC) is the third most common malignancy worldwide, with more than 1.9 million new cases reported annually. Survival among patients with CRC depends on several factors, including disease stage at diagnosis, the patient's clinical condition, tumour characteristics, and treatment modalities. Despite advances in surgical techniques, active involvement in clinical, translational, and basic research, and improvements in perioperative care, substantial disparities in short- and long-term outcomes persist across healthcare providers and countries. To reduce these variations and improve the quality of cancer care, several metrics have been used to evaluate hospitals, therapeutic approaches, and surgical outcomes. In response to these needs, a composite measure known as "Textbook Outcome" (TO) was developed. It encompasses multiple favourable outcomes and requires patients to meet all essential quality-of-care criteria for a given procedure. TO serves as an effective predictor of survival and is recognised as an indicator of the quality of hospital care. This study aims to investigate the value of TO as an indicator of clinical outcomes and quality of care in the surgical treatment of colorectal cancer. The primary objective is to assess the achievement of Textbook Outcome criteria in colorectal cancer surgery performed by Italian surgeons. Textbook Outcome is defined by the fulfilment of six key parameters: in-hospital survival, defined as the absence of death during hospitalisation or within 30 days after surgery; radical resection, defined as an R0 resection with at least 12 lymph nodes examined; absence of reoperation; absence of an unplanned stoma; absence of major adverse events, classified according to the Clavien-Dindo criteria as grade III or higher, within 30 days after surgery; and a hospital length of stay of 14 days or less without unplanned readmission. The simultaneous achievement of all six parameters constitutes the optimal outcome, defined as Textbook Outcome. The secondary objective is to assess the consistency with which surgeons meet TO criteria during colorectal surgery and to identify patient- and procedure-related factors associated with failure to achieve TO. Through a detailed analysis of these factors, the study aims to identify the variables influencing TO failure and to determine which aspects of clinical practice or patient characteristics represent the main barriers to meeting these quality standards. The usefulness of TO as a quality indicator in the surgical management of colorectal cancer will also be evaluated by examining which individual unmet components are most frequently associated with unfavourable clinical outcomes, with particular attention to the different clinical presentations of the disease. The study will include all adult patients admitted to the participating surgical departments with a diagnosis of colorectal cancer between 1 January 2022 and 31 December 2024. Patient data will be analysed retrospectively. Demographic characteristics, comorbidity status, clinical and radiological findings, treatment strategies, and 30-day morbidity and mortality will be evaluated. Data will be entered into an online database between 1 January 2025 and 31 May 2025. The study will last 12 months: the first five months will be dedicated to data collection and the subsequent seven months to data analysis. The study is scheduled to begin in January 2025 with the commencement of data collection. The sample size required to achieve 80% statistical power, with a margin of error of ±5% at a 95% confidence level, is 324 patients. Continuous variables not following a normal distribution will be expressed as medians with interquartile ranges (IQRs), whereas normally distributed continuous variables will be reported as means with standard deviations (SDs). The Mann-Whitney U test will be used to compare non-normally distributed continuous variables between groups. Normally distributed continuous variables will be compared using the independent-samples t-test or one-way analysis of variance (ANOVA), as appropriate. Categorical variables will be reported as frequencies, and proportions will be compared between groups using the χ² test. Survival curves will be estimated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors for survival will be assessed using multivariable Cox proportional hazards regression. Statistical significance will be set at a two-sided P value of \< .05.

Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Cancer Patients

This is a Phase 2 study designed to determine the preliminary anti-tumor activity and confirm the safety of VV1 in combination with cemiplimab. The study will enroll patients with three distinct separate tumor cohorts. The cancers types are colorectal, head and neck carcinoma, and melanoma that are progressing on CPI treatment. (CRC and melenoma cohorts are now closed to new patients)

Colorectal Cancer Screening Outreach

This is a 4 arm pragmatic trial to test a multicomponent intervention designed to improve adherence to colorectal cancer screening.

The French E3N Prospective Cohort Study

The French E3N cohort was initiated in 1990 to investigate the risk factors associated with cancer and other major non-communicable diseases in women. The participants were insured through a national health system that primarily covered teachers, and were enrolled from 1990 after returning baseline self-administered questionnaires and providing informed consent. The cohort comprised nearly 100 000 women with baseline ages ranging from 40 to 65 years. Follow-up questionnaires were sent approximately every 2-3 years after the baseline and addressed general and lifestyle characteristics together with medical events (cancer, cardiovascular diseases, diabetes, depression, fractures and asthma, among others). The follow-up questionnaire response rate remained stable at approximately 80%. A biological material bank was generated and included blood samples collected from 25 000 women and saliva samples from an additional 47 000 women. Ageing among the E3N cohort provided the opportunity to investigate factors related to agerelated diseases and conditions as well as disease survival.

A Phase II Platform Study to Evaluate Treatment With Cemiplimab Monotherapy or Cemiplimab Plus Fianlimab or Other Novel Combinations in Patients With Colorectal Cancer With Minimal Residual Disease Following Definitive Surgery and Chemotherapy (EMPIRE)

The NSABP FC-13 study is being done to determine if using immunotherapies alone or in combination with other drugs will delay or prevent colorectal cancer from coming back in patients with colorectal cancer who are ctDNA-positive after their treatment. Immunotherapeutic drugs (immunotherapies) act on different proteins on the surface of cells of the immune system and trigger the immune system to destroy cancer cells. The drugs being studied in NSABP FC-13 are cemiplimab, fianlimab, and REGN7075.

Prehabilitation in High-risk Oncologic Surgery

The goal of this clinical study is to learn whether a prehabilitation program can improve recovery after major abdominal surgery in adults with cancer who are receiving treatment before surgery. Prehabilitation is supportive care given before surgery to help patients prepare physically, nutritionally, and emotionally. The main questions this study aims to answer are: 1. Does prehabilitation reduce the number of participants who die or have serious complications within 30 days after surgery? 2. Does prehabilitation improve physical strength and fitness, nutritional status, emotional well-being, and quality of life before surgery? 3. Does prehabilitation affect the length of the hospital stay after surgery, the time it takes to start additional cancer treatment after surgery, or the ability to complete recommended additional treatment? Participants will take part in a prehabilitation program during their treatment period before surgery. The program includes visits with physical therapy, nutrition, and health psychology. Participants will meet with each specialty at least twice before surgery. They will also complete questionnaires and tests that measure physical function, diet and weight, emotional well-being, and quality of life. After surgery, information about recovery and additional cancer treatment will be collected from medical records for up to 120 days. Researchers will compare the outcomes of participants who receive the prehabilitation program with outcomes from similar patients who previously received care at Fox Chase Cancer Center but did not participate in this study.

The Impact of AI-Assisted Nursing Care Intervention Within the Enhanced Recovery Framework on Outcomes of Colorectal Surgery Patients

Colorectal cancer is one of the most common cancers worldwide, affecting a large number of people each year (Bray et al., 2022). Surgical intervention remains the gold standard in treatment. However, advances in surgical techniques and increased effectiveness of neoadjuvant therapies have brought sphincter-preserving surgeries to the forefront, reducing the need for stoma creation compared to the past (Jo \& Wilson, 2025; Wang et al., 2025). Even without stoma creation, these patients face complex care needs in the post-discharge period, including changes in bowel habits, nutritional management, and adaptation to physical activity (Wang et al., 2025). Difficult-to-manage complications carry a high risk of readmission to the hospital. Patients receive limited support during the transition from the hospital to home and at home (Storm et al., 2024). Patients and their families are often left alone to manage home care until routine follow-up appointments. Patients, especially those poorly prepared for discharge, may not know how to perform care practices at home or what to watch out for in case of complications. Situations that are well managed in the hospital can spiral out of control upon inadequate follow-up after the patient returns home, leading to unplanned readmissions. Insufficient postoperative patient follow-up can cause anxiety in patients, leading to readmissions due to the inability to manage the home care process effectively (Storm et al., 2024). Although accelerated recovery after surgery (ERAS) is known to shorten hospital stays (Gustafsson et al., 2025; Gustafsson et al., 2019), studies show varying results regarding readmissions, re-operations, developing complications, and survival (Coleman et al., 2006; Takchi et al., 2020; Lee et al., 2022). These variable results highlight the need for a structured discharge process and home care management for patients who undergo ERAS and are discharged home earlier. In the study by Takchi et al. (2020), a scheduled phone call was proposed as the final step in advanced recovery recommendations and presented as a pilot study. The study reported that each patient contacted reported at least one symptom and personal care need (Takchi et al., 2020). The scheduled phone calls proposed by Takchi et al. (2020) are an important monitoring mechanism in the recovery process; however, they are insufficient. Supporting this monitoring process with a structured discharge management and AI-powered digital video accessible to the patient at any time, extends the continuity of care to a digital dimension. It is reported that AI-powered multimedia tools, whose use is increasing with the transformation in health technologies today, reduce cognitive load by concretizing complex surgical processes with audiovisual materials and improve patients' self-care skills regardless of their health literacy level (Mendoza-Pinto et al., 2025). "Content prepared with generative artificial intelligence algorithms, in particular, increases the retention of information and the patient's digital health literacy compared to traditional educational materials (Zaretsky et al., 2024). This study aims to both structure the discharge and post-discharge follow-up process, which is included in ERAS protocols to a limited extent, and to increase the patient's readiness for discharge, improve patient outcomes, and facilitate home care management using AI-assisted educational videos. Thus, the study significantly points to a fourth step, which is included in ERAS guidelines in the pre-operative, intra-operative, and post-operative phases and is felt to be missing: the discharge and home follow-up process.

The AIDPRO-CRC Trial

The AIDPRO-CRC trial aims to improve outcomes for patients undergoing surgery for colorectal cancer by using artificial intelligence (AI) to assist surgeons in risk assessment. The trial will evaluate whether AI can help surgeons better predict the risk of complications and death, leading to improved care, fewer complications, and better use of healthcare resources. In this nationwide, randomized clinical trial, participants will be divided into two groups. One group will have their risk assessed by a surgeon using standard clinical methods, while the other group will have their risk assessed by a surgeon using AI assistance. Based on the risk level, patients will receive varying levels of perioperative care. The AI-assisted risk assessment aims to tailor the treatment more precisely to each patient's individual needs, precisely allocating care to those who need it to more efficiently allocate heath system resources while having no deterioration in patient outcomes. The primary hypothesis is that AI-assisted risk assessment will lead to more efficient and economic patient care without a deterioration in patient outcomes. The trial also aims to explore clinician satisfaction with the platform and its perceived effect. This is paired with a substudy exploring the variability of suggested treatment plans by clinicians with and without access to the MDT presentation platform. The trial will include patients at seven hospitals across Denmark, involving patients diagnosed with colorectal cancer who are scheduled for curative surgery. All patients will receive standard treatment according to national guidelines, with the only difference being the modality of risk assessment. For the evaluation of the clinicians satisfactory with the device and the substudy of variability of suggested treatment plans, the trial will enroll clinicians using the device. This study is a researcher-initiated, nationwide, randomized clinical trial involving patients diagnosed with colorectal cancer across eight hospitals in Denmark. Participants will be randomly assigned to one of two groups: AI-assisted risk assessment or standard surgeon-led assessment. The intervention focuses on optimizing perioperative care based on individual risk levels determined by either AI or the surgeon's clinical judgment. The study builds on a successful pilot project (AID-SURG) that showed promising results in reducing complications, hospital stays, and readmissions.

Evaluation of SINGLE PORT (SP) Robotic Technology in Colorectal Surgery

Currently a multiport robotic surgery platform (Intuitive Xi) is widely available and used for colorectal surgery indications. A Single port platform (Intuitive SP) is FDA approved for Head and Neck and Urology but has not been widely used in colorectal surgery. This study seeks to evaluate the safe and effective use of the SP platform for colorectal surgery indications.

A First in Human Study of ALX2004 With Advanced or Metastatic Selected Solid Tumors

A Phase 1, First in Human, Open-Label Multicenter Study to Evaluate ALX2004, an Antibody Drug Conjugate Targeting EGFR in Participants with Advanced or Metastatic Select Solid Tumors

Single-stapled Double Purse-string Technique for Colorectal Anastomosis

A single-arm, single-center prospective study of a novel double purse-string technique for constructing the colorectal anastomosis in robot-assisted laparoscopic resection of the sigmoid colon for cancer.

ctDNA-guided Surveillance for Stage III CRC, a Randomized Intervention Trial

IMPROVE-IT2 is a randomized multicenter trial comparing the outcomes of ctDNA guided post-operative surveillance and standard-of-care CT-scan surveillance. The hypothesis of this study is that ctDNA guided post-operative surveillance combining ctDNA and radiological assessments could result in earlier detection of recurrent disease and identify more patients eligible for curative treatment.

Clinicopathological Characteristics of Colon Cancer in Young Age

A Study on the Characteristics of Colorectal Cancer by Age and sex.

Akkermansia Probiotics Plus Anti-PD-1 Monoclonal Antibody in MSS/pMMR Advanced Colorectal Cancer

The investigators propose to conduct a single-center, single-arm, Phase I clinical study to explore the safety and feasibility of Akkermansia probiotics combined with anti-PD-1 monoclonal antibody in patients with MSS/pMMR advanced colorectal cancer, as well as its impact on gut microbiota and the immune microenvironment.

FULIRI Plus Targeted Therapy for First-line Conversion Therapy of Colorectal Cancer Liver Metastases.

This study is a single-center, prospective, randomized, single-arm phase II clinical trial designed to evaluate the safety and efficacy of FULIRI chemotherapy regimen combined with targeted therapy (bevacizumab/cetuximab) as first-line conversion therapy for colorectal cancer with liver metastases. Eligible patients with colorectal cancer and liver metastases, after signing informed consent, received FULIRI chemotherapy combined with bevacizumab/cetuximab targeted therapy. Efficacy was assessed after every four treatment cycles, followed by multidisciplinary team (MDT) discussion regarding potential surgical resection, ablation, or stereotactic radiotherapy. The primary endpoint was the objective response rate (ORR), and secondary endpoints included: disease control rate (DCR), R0 resection rate of liver metastases, progression-free survival (PFS), 3-year/5-year survival rates, and the incidence of acute toxicities of any grade and grades 3/4.

Shared Decision-Making for Colorectal Cancer Screening in High-Risk First-Degree Relatives Aged 40-49

The primary objective of this study was to evaluate the impact of a constructed shared decision (SDM) intervention (offering an option between colonoscopy and immunochemical collapsible occult blood testing (fecal immunochemical test; FIT)) on improving the incidence of high colonoscopy stromal in patients aged 40-49 years with a close relative suffering from colorectal cancer, compared to standard care (direct referral for colonoscopy).

Shield Post-Approval Study Protocol

The Shield post-approval study (PAS) is a prospective, longitudinal study supplemented with Real World Evidence (RWE) to evaluate the longitudinal performance of Shield in an average risk population at a second round of testing for individuals between the ages of 45 and 81 at average risk of CRC using colonoscopy as the reference method.

Optimal Surveillance Strategy After Positive FIT and Negative Colonoscopy

Individuals with high fecal hemoglobin concentrations detected by fecal immunochemical testing (FIT) but negative findings on high-quality colonoscopy represent a clinically challenging population. Although colonoscopy is considered the gold standard diagnostic procedure, previous studies suggest that these individuals may still have an elevated long-term risk of colorectal cancer. This randomized controlled trial aims to determine the optimal surveillance strategy for this high-risk group by comparing two approaches: repeat FIT testing after two years versus direct colonoscopy after two years.

A Study of Biological, Genetic, and Constitutional Factors and Non-invasive Monitoring to Assess Personal Cancer Risks

The PRO-ACTIVE study aims to develop a clinical-translational program in the field of cancer prevention in all its phases (primary, secondary, and tertiary) to intervene before the clinical and radiological manifestation of the disease. It starts with risk prediction and leads to early diagnosis of the disease or recurrence in the subclinical phase. The PRO-ACTIVE study includes the following activities: * WP1: Integrated DNA-RNA approach for the identification of hereditary markers of predisposition to tumors * WP2: Global biological and molecular analysis of the host and tumor for the prevention and monitoring of recurrences * WP3: Analysis of the immunological status for the diagnosis of primary prevention and relapses in correlation to genetic and environmental factors * WP4: Study of the tumor microenvironment for recurrence prediction

EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer

The purpose of this study is to determine the immunogenicity of the CIMAvaxEGF® vaccine (that is, its effectiveness in inducing an anti-tumor immune response) in patients with metastatic KRAS/NRAS/BRAF wild-type gene colorectal cancer, when given in combination with standard therapies used in the treatment of advanced colorectal cancer.

Liquid Biopsy and Machine Learning for Early Colorectal Cancer, Adenomas, Lynch Cancers, and Residual Disease Detection

This is an multicenter study that will test the diagnostic accuracy of a blood test (i.e., a liquid biopsy) for the diagnosis of colorectal cancer (CRC), advanced adenomas (AAs), as well as Lynch-syndrome associated cancers. Additionally, a pre-planned analysis will evaluate the use of this liquid biopsy as a tool for molecular residual disease monitoring purposes.

Serum Talin-1 and Cripto-1 in Colorectal Cancer

The goals of this study are * To evaluate the clinical utility of Talin-1 and Cripto-1 measurement in colorectal cancer patients in comparison with healthy controls. * To Compare the diagnostic significance of serum Talin-1 and Cripto-1 with traditional serum biomarker CEA

Phase 1/2 Dose Finding, Safety and PK Study in Advanced Refractory Solid Tumors

This is a multicenter, open-label FIH, Phase 1a (dose escalation), Phase 1b (dose expansion) and Phase 2 study in patients with advanced metastatic solid tumors refractory to standard treatment.

Stereotactic Ablative Radiotherapy (SABR) for the Treatment of Patients With Metastatic Cancer, ID-COMET Trial

This protocol is comprised of three unblinded, randomized, single-center studies to evaluate the impact of immediate versus three-month delayed comprehensive ablative treatment on survival in newly diagnosed metastatic patients with lung (Trial 1), colorectal (Trial 2), and prostate (Trial 3) cancers