Clinical Research Directory

Adjuvant mFOLFIRINOX for High-risk Stage III Colon Cancer

A multicenter, open labeled randomized, phase II trial comparing mFOLFIRINOX and mFOLFOX6 as adjuvant treatment for high risk stage III (pT4N1/2 or pTanyN2) colon cancer

Virtual Reality for GI Cancer Pain to Improve Patient Reported Outcomes

Patients with digestive tract malignancy often experience severe and unremitting abdominal pain that negatively affects physical, emotional, and social function, as well as health related quality of life (HRQOL). Therapeutic virtual reality (VR) has emerged as a promising and evidence-based treatment modality for cancer pain. Users of VR wear a pair of goggles with a close-proximity screen in front of the eyes that creates a sensation of being transported into lifelike, three-dimensional worlds. To date, VR has been limited to short-term clinical trials for cancer pain. Moreover, limited research exists on theory-based VR modalities beyond mere distraction, such as VR that employs acceptance and commitment therapy (ACT) with components of biofeedback and mindfulness. To bridge these gaps, this study seeks to: (1) assess the impact of immersive VR on patient-reported outcomes (PROs), including pain, activity metrics, and opioid use among patients with visceral pain from a digestive tract malignancy; (2) assess differences in PROs, activity metrics, and opioid use between skills-based VR therapy vs. distraction VR therapy; and (3) determine patient-level predictors of VR treatment response in visceral cancer pain. To address these aims, the study will measure PROs and opioid use in 360 patients randomized among 3 groups and follow them for 60 days after enrollment: (1) an enhanced VR group receiving skills-based VR; (2) a distraction-based VR group receiving patient-selected VR videos; and (3) a VR sham control group using a VR headset with 2-D content. The results will inform best practices for the implementation of VR for visceral cancer pain management and guide selection of patient-tailored experiences.

Phase II Study of Neoadjuvant Dostarlimab in Patients With Untreated T3-4N0-2 or Stage III pMMR/MSS Resectable Colon Cancer

Dostarlimab belongs to a class of drugs called PD-1 inhibitors that use your own immune system to treat cancer (immunotherapy). It is designed to stop cancer from growing by helping your immune system recognize and fight the cancer. This investigational medicinal product (IMP) has been approved by the Belgian authorities, but not for the treatment of colon cancer. It is known that a small number of patients with pMMR/MSS colon cancer may have significant response to medication of this type (immunotherapy) depending on each person's biology. Trial intervention for all patients will be neo-adjuvant dostarlimab 500 mg IV, given alone by intravenous infusion. Two administrations of dostarlimab are foreseen, at three weeks interval, before surgery for your colon cancer. It has not yet been proven that this treatment can cure, improve or stabilise your disease or condition. The study aims to investigate specific molecular changes in tumour and blood after dostarlimab monotherapy administered and before surgery which could be associated with improved response to conventional treatment in some patients. If you decide to participate, as the duration of treatment with dostarlimab is 6 weeks, surgery may be slightly delayed compared to patients that are not treated with dostarlimab and go directly for surgery. It remains uncertain if this is beneficial in your personal situation but some patients might experience significant response. The risks have been carefully assessed and the potential benefits for some patients are considered important and justify undertaking the treatment. Subsequent therapy after surgery remains at the discretion of the treating physician. The duration of a patient on trial will last up to 4 months from the first dose of dostarlimab and afterwards 2 years of follow up is applicable.

The Sagittarius Trial

Background \& Rationale: Colon cancer is a leading cause of cancer deaths, with a high recurrence rate in stage II high-risk and stage III patients due to undetectable micro-metastases. Liquid biopsy (LB) detects residual cancer DNA post-surgery and monitors treatment response. Primary Objective: Show that therapy based on tumor genetics and LB improves outcomes and quality of life for high-risk stage II and stage III colon cancer patients compared to conventional therapy. Secondary Objectives: Compare recurrence times. Evaluate side effects and quality of life. Assess cost differences. Validate LB accuracy. Study Design: Patients are randomized into standard or personalized treatment groups based on LB results. For positive LB results: Randomized to standard or customized therapy. Monitor treatment response with LB. For negative LB results: Randomized to standard chemotherapy or follow-ups, starting treatment if a positive result appears. Treatments: Standard Chemotherapy: CAPOX (capecitabine and oxaliplatin) FOLFOX (folinic acid, fluorouracil, and oxaliplatin) Personalized Treatments: Customized chemotherapy with CAPOX. Immunotherapy with nivolumab and ipilimumab. Targeted therapy with trastuzumab and pertuzumab. FOLFOX with anti-EGFR (epidermal growth factor receptor) therapy (panitumumab). Population: 700 patients with operable stage III and high-risk stage II colon cancer. Inclusion Criteria: Aged 18 or older. Confirmed diagnosis. Tumor tissue sample available. Exclusion Criteria: History of other tumors within five years. Metastatic disease or recent experimental study participation. Major cardiovascular diseases, intestinal obstruction, autoimmune diseases, neuropathy, HIV (Human Immunodeficiency Virus), active TB (Tuberculosis), or hepatitis B/C infection. Medical conditions contraindicating treatment. Prior neoadjuvant treatment administered before surgery. Endpoints: Primary: Evaluate disease recurrence after two years. Secondary: Assess disease recurrence and overall survival at 3 and 5 years. Measure treatment safety and tolerability. Validate LB accuracy. Monitor quality of life using questionnaires. The study will last 5 years and be conducted in 25-30 hospitals across Italy, Spain, and Germany.

Neoadjuvant FOLFOXIRI Versus Immediate Surgery for Stage II and III Colon Cancers

BACKGROUND: In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become a standard treatment. However, 20 to 30 % of these patients will develop distant metastasis, which ultimately result in death. Perioperative chemotherapy is a promising strategy with potential benefits that could be more effective at eradicating micrometastases. Moreover, shrinking tumor before surgery not only facilitate removal of all the tumor by the surgeon but also reduce tumor cell spreading during the procedure. With recent advances in radiology, preoperative computed tomography allows a good prediction of tumor stage (wall penetration and nodal involvement) prior to surgery. The investigators conducted the present randomized study to explore whether perioperative chemotherapy with FOLFOXIRI regimen compared with postoperative chemotherapy could improve disease-free survival in patients with radiologically staged, High-risk, but resectable Stage II or III colon cancer. OBJECTIVE: The primary objective of this study is to evaluate the efficacy of perioperative chemotherapy with FOLFOXIRI regimen compared to postoperative chemotherapy in patients with High-risk Resectable Stage II and III colon cancer. Secondary objectives are efficacy in terms of R0 resection rate, overall survival (OS), relapse-free survival (RFS), down-staging of primary tumors, and tolerability of perioperative therapy and postoperative complications.