Fruquintinib Combined With Sintilimab ± Radiotherapy for Third-line Treatment of Colorectal Cancer With Liver Metastases

NCT ID: NCT06356584

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2026-10-01

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.

Conditions

Colorectal Cancer; Immunotherapy; Radiotherapy; Targeted Therapy; Liver Metastasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immunotherapy, targert therapy, and radiotherapy

For liver oligometastases, high-dose stereotactic body radiation therapy (SBRT) irradiation will be administered to all lesions with a dose fractionation pattern of 40-50 Gy/5F, 60-70 Gy/10F, or 65 Gy/13F. For multiple liver metastases, SBRT plus low-dose radiation therapy (LDRT) will be performed to all lesions. One or more suitable lesions (which will be selected by the physician based on proximity to organs at risk) will undergo SBRT with a dose fractionation pattern of 40-50 Gy/5F, 60-70 Gy/10F, or 65 Gy/13F, and the remaining lesions will undergo LDRT at a total dose of 1-10 Gy at 0.5-2.0 Gy/F. Extrahepatic lesions will be not treated with radiotherapy. Targeted therapy and immunotherapy will be administered one week after the end of radiation therapy. A 21-day treatment cycle of sintilimab (200 mg, D1, once every 3 weeks) will be given intravenously on day 1 of each cycle, and fruquintinib will be given on days 1 to 14.

Group Type: EXPERIMENTAL

Immunotherapy (Sintilimab)

Intervention Type: DRUG

Sintilimab

Targeted Therapy Agent (Fruquintinib)

Intervention Type: DRUG

Fruquintinib

Radiotherapy (SBRT and LDRT)

Intervention Type: RADIATION

SBRT and LDRT

Immunotherapy and targert therapy

A 21-day treatment cycle of sintilimab (200 mg, D1, once every 3 weeks) will be given intravenously on day 1 of each cycle, and fruquintinib will be given on days 1 to 14.

Group Type: ACTIVE_COMPARATOR

Immunotherapy (Sintilimab)

Intervention Type: DRUG

Sintilimab

Targeted Therapy Agent (Fruquintinib)

Intervention Type: DRUG

Fruquintinib

Targert therapy

Treatment with fruquintinib (5 mg, po, D1-21, once every 4 weeks) will be given on days 1 through 21 in a 28-day treatment cycle.

Group Type: ACTIVE_COMPARATOR

Targeted Therapy Agent (Fruquintinib)

Intervention Type: DRUG

Fruquintinib

Interventions

Immunotherapy (Sintilimab)

Sintilimab

Intervention Type: DRUG

Targeted Therapy Agent (Fruquintinib)

Fruquintinib

Intervention Type: DRUG

Radiotherapy (SBRT and LDRT)

SBRT and LDRT

Intervention Type: RADIATION

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shandong Cancer Hospital and Institute

OTHER

Sponsor Role: lead

Responsible Party

Jinbo Yue

Shandong Cancer Hospital Ethics Committee

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jin Bo Yue

Role: PRINCIPAL_INVESTIGATOR

Shandong Cancer Hospital and Institute

Locations

Jinbo Yue

Jinan, Shandong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jin Bo Yue, dorctor

Role: CONTACT

Len.Xu@hotmail.com

0531-67626442 ext. 0531-67626442

Facility Contacts

Jin Bo Yue

Role: primary

Len.Xu@hotmail.com

0531-67626442 ext. 0531-67626442

Other Identifiers

SDZLEC2024-078-01

Identifier Type: -

Identifier Source: org_study_id