protocolSection identificationModule nctId: NCT06356584, orgStudyIdInfo id: SDZLEC2024-078-01, briefTitle: Sintilimab Combined With Fruquintinib/Regorafenib ± Radiotherapy for Third-line Treatment of Advanced Metastatic Colorectal Cancer, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-04-01, primaryCompletionDateStruct date: 2026-10-01, completionDateStruct date: 2026-10-01, studyFirstPostDateStruct date: 2024-04-10, lastUpdatePostDateStruct date: 2024-04-10, sponsorCollaboratorsModule leadSponsor name: Shandong Cancer Hospital and Institute, class: OTHER, descriptionModule briefSummary: Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. Its early clinical manifestations are often subtle, leading to late-stage diagnosis in about 30% of cases with distant metastases. Liver metastases are widespread and associated with poor prognosis, especially in terms of response to immunotherapy. Despite advancements in first- and second-line treatments, third-line therapies for advanced CRC remain limited, emphasizing the need for novel strategies. This prospective study evaluates the efficacy of combined therapy involving Sintilimab, Fruquintinib/Regorafenib, and radiotherapy in advanced CRC. The study cohort comprises patients with non-liver metastatic advanced CRC and those with liver metastases, each receiving tailored treatment protocols. The primary objectives are to assess progression-free survival (PFS), overall survival (OS), and treatment response rates. Subgroup analyses will focus on liver metastases to delineate their impact on treatment outcomes. The rationale for this study stems from the intricate interplay between immunotherapy, targeted therapy, and radiotherapy in CRC management. Previous data suggest a negative correlation between liver metastases and immunotherapy efficacy, necessitating a comprehensive approach integrating multiple treatment modalities. Radiotherapy, particularly stereotactic body radiation therapy (SBRT), has shown promise in controlling liver tumors and modulating the tumor microenvironment, potentially enhancing immunotherapy responses. This study aims to provide valuable insights into optimizing third-line and subsequent therapies for advanced CRC by elucidating the efficacy and safety of this combined treatment approach. The findings may pave the way for personalized treatment strategies tailored to individual patient characteristics, ultimately improving clinical outcomes in this challenging disease setting., conditionsModule conditions: Colorectal Cancer, conditions: Immunotherapy, conditions: Radiotherapy, conditions: Targeted Therapy, designModule studyType: INTERVENTIONAL, phases: PHASE2, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 141, type: ESTIMATED, armsInterventionsModule interventions name: Sintilimab, outcomesModule primaryOutcomes measure: Progression-free survival (PFS), secondaryOutcomes measure: Overall response rate (ORR), secondaryOutcomes measure: Disease control rate (DCR), secondaryOutcomes measure: Overall survival (OS), eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 75 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Jinbo Yue, status: RECRUITING, city: Jinan, state: Shandong, zip: 250000, country: China, contacts name: Jin Bo Yue, role: CONTACT, phone: 0531-67626442, phoneExt: 0531-67626442, email: Len.Xu@hotmail.com, geoPoint lat: 36.66833, lon: 116.99722, hasResults: False