Colorectal Cancer, Immunotherapy, Radiotherapy, Targeted Therapy, Liver Metastasis
Conditions
Keywords
Colorectal cancer, Immunotherapy, Radiotherapy, Targeted therapy, Liver metastasis
Brief summary
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. This prospective study will evaluate the efficacy of combined therapy involving sintilimab, fruquintinib, and radiotherapy in CRC with liver metastases. The primary objectives are to assess progression-free survival, overall survival, and treatment response rates. This study aims to provide valuable insights into optimizing third-line and subsequent therapies for CRC with liver metastases by elucidating the efficacy and safety of this combined treatment approach.
Detailed description
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. This prospective study will evaluate the efficacy of combined therapy involving sintilimab, fruquintinib, and radiotherapy in CRC with liver metastases. The primary objectives are to assess progression-free survival, overall survival, and treatment response rates. 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, 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 CRC with liver metastases by elucidating the efficacy and safety of this combined treatment approach.
Interventions
Sintilimab
DRUGTargeted Therapy Agent (Fruquintinib)
Fruquintinib
RADIATIONRadiotherapy (SBRT and LDRT)
SBRT and LDRT
Sponsors
Shandong Cancer Hospital and Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* ECOG PS 0-2 * Histologically confirmed colorectal adenocarcinoma with liver metastases (8th edition AJCC) * MSS/pMMR subtype * Previously received standard first- and second-line systemic anti-tumor therapy * At least one measurable lesion as defined by RECIST 1.1 criteria * Access to tumor samples for biomarker assessment * Expected survival of ≥3 months * Normal function of major organ systems (within 14 days before enrollment) * No systemic corticosteroid treatment within 7 days before treatment initiation, excluding physiological corticosteroid replacement therapy. * Fertile males or females with the potential for pregnancy must use highly effective contraception methods during the trial.
Exclusion criteria
* Patients diagnosed with malignancies other than colorectal cancer within 3 years prior to enrollment. * Participating in an interventional clinical study or receiving other investigational drugs or treatments with study devices within the past 4 weeks before enrollment. * Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs targeting another T cell co-stimulatory or co-inhibitory receptor (e.g., CTLA-4, OX-40, CD137), fruquintinib, etc. * Received traditional Chinese medicine or immune-modulating drugs with anti-tumor indications within the past 2 weeks before enrollment (excluding local use for controlling pleural effusion). * Experienced active autoimmune diseases requiring systemic therapy within the past 2 years before enrollment. Replacement therapy is not considered systemic therapy. * Diagnosed with immune deficiency or received systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of investigational treatment. After consultation with the sponsor, the use of physiological doses of corticosteroids may be approved. * Received liver radiotherapy within the past 2 weeks before enrollment. * Known presence of central nervous system metastases and/or carcinomatous meningitis. * Received systemic corticosteroid therapy within 7 days before enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 1 year | Time from initial drug administration to first radiographic disease progression or death (whichever occurs first). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | 1 year | The proportion of subjects achieving complete response (CR) and partial response (PR) among the total subjects; includes assessment of both irradiated and non-irradiated lesions. |
| Disease control rate (DCR) | 1 year | The proportion of subjects achieving complete response (CR), partial response (PR), and stable disease (SD) among the total subjects. |
| Overall survival (OS) | 3 year | Time from initial drug administration to death of the subject for any reason. |
| The incidence and grade of adverse events | 2 year | Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. |
Countries
China
Contacts
Primary ContactJin Bo Yue, dorctor
Outcome results
None listed