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

NCT06356584 | Recruiting Phase 2

• 1 other identifier: SDZLEC2024-078-01
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Colorectal cancer; Immunotherapy; Radiotherapy; Targeted therapy; Liver metastasis

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Time from initial drug administration to first radiographic disease progression or death (whichever occurs first).

  1 year

Secondary Outcomes (4)

• Overall response rate (ORR)

  1 year

• Disease control rate (DCR)

  1 year

• Overall survival (OS)

  3 year

• The incidence and grade of adverse events

  2 year

Study Arms (3)

Immunotherapy, targert therapy, and radiotherapy

EXPERIMENTAL

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.

Drug: Immunotherapy (Sintilimab); Drug: Targeted Therapy Agent (Fruquintinib); Radiation: Radiotherapy (SBRT and LDRT)

Immunotherapy and targert therapy

ACTIVE COMPARATOR

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.

Drug: Immunotherapy (Sintilimab); Drug: Targeted Therapy Agent (Fruquintinib)

Targert therapy

ACTIVE COMPARATOR

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.

Drug: Targeted Therapy Agent (Fruquintinib)

Interventions

Immunotherapy (Sintilimab) DRUG

Sintilimab

Immunotherapy and targert therapy; Immunotherapy, targert therapy, and radiotherapy

Radiotherapy (SBRT and LDRT) RADIATION

SBRT and LDRT

Immunotherapy, targert therapy, and radiotherapy

Targeted Therapy Agent (Fruquintinib) DRUG

Fruquintinib

Immunotherapy and targert therapy; Immunotherapy, targert therapy, and radiotherapy; Targert therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Jinbo Yue

Jinan, Shandong, 250000, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Immunotherapy; sintilimab; HMPL-013; Radiotherapy; Radiosurgery

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jin Bo Yue

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Bo Yue, dorctor

CONTACT

0531-67626442; Len.Xu@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Shandong Cancer Hospital Ethics Committee

Study Record Dates

• First Submitted: April 5, 2024
• First Posted: April 10, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)