Combination of High and Low-Dose Radiotherapy With Immune Therapy and TKI in Advanced Colorectal Cancer: A Phase II Study

Summary

The goal of this clinical trial is to learn whether a high- and low-dose radiotherapy regimen followed by anti-angiogenic TKI and anti-PD-1 antibody therapy works to treat advanced metastatic colorectal cancer. It will also evaluate long-term survival outcomes and explore potential biomarkers associated with tumor response and immune modulation.

The main questions it aims to answer are:

Does the high- and low-dose radiotherapy regimen followed by sequential anti-angiogenic TKI and anti-PD-1 therapy improve the objective response rate (ORR) in patients with advanced metastatic colorectal cancer?

What are the disease control rate (DCR) and survival outcomes following this treatment strategy?

Are tumor response and long-term survival associated with specific biomarkers related to systemic immune modulation induced by radiotherapy to different metastatic organs?

How does this radiotherapy pattern affect tumor immune infiltration in metastatic lesions?

This is a single-arm, single-center, prospective Phase II clinical study designed to evaluate the efficacy of a high- and low-dose radiotherapy regimen targeting metastatic lesions followed by sequential anti-angiogenic TKI and anti-PD-1 antibody therapy in patients with advanced metastatic colorectal cancer.

Participants will:

Receive high- and low-dose radiotherapy to metastatic lesions. Subsequently receive anti-angiogenic TKI combined with anti-PD-1 antibody therapy.

Undergo regular clinical assessments and imaging evaluations to determine tumor response.

Provide blood and tumor samples for biomarker and immune infiltration analysis. Be followed for survival outcomes and disease progression.

Conditions

• Refractory Colorectal Cancer
• Radiotherapy-Induced Immune Priming
• Immune Response

Interventions

RADIATION

High- and Low-Dose Radiotherapy

Participants will receive a stratified high- and low-dose radiotherapy regimen to metastatic lesions based on lesion size, followed by sequential anti-angiogenic tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody therapy. Metastatic lesions with a maximum diameter ≤2 cm will be treated with stereotactic body radiotherapy (SBRT) at 8 Gy per fraction for 3 consecutive fractions (total dose 24 Gy) prior to initiation of the first cycle of targeted and immunotherapy. The total cumulative volume of lesions treated with SBRT will not exceed 100 cm². Metastatic lesions with a maximum diameter \>2 cm will receive low-dose radiotherapy (LDRT) at 3 Gy per fraction for 5 fractions. LDRT will be administered rhythmically, with one fraction delivered prior to each cycle of targeted and immunotherapy, for a total of five fractions. The total cumulative volume of lesions treated with LDRT will not exceed 500 cm². Within 7 days after completion of radiotherapy, participants will initiate systemi

DRUG

Anti-Angiogenic TKI and Anti-PD-1 Therapy

Participants will receive systemic therapy consisting of an oral anti-angiogenic tyrosine kinase inhibitor (TKI) in combination with an intravenous anti-PD-1 monoclonal antibody. The anti-angiogenic TKI will be administered orally according to the approved dosing schedule. The anti-PD-1 antibody will be administered intravenously at standard dosing intervals. Treatment will begin within 7 days after completion of radiotherapy and will continue until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. Safety will be monitored throughout treatment, and adverse events will be graded according to CTCAE version 5.0.

Sponsors & Collaborators

• Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-01

Primary Completion

2028-04-01

Completion

2029-04-01