Postoperative Chemotherapy With/Without Radiotherapy and Immunotherapy for Colorectal Liver Metastases With High Risk of Locally Recurrence (IMPROVE)

Postoperative Chemotherapy With/Without Radiotherapy and Immunotherapy for Colorectal Liver Metastases With High Risk of Locally Recurrence: A Randomized Controlled Phase II Trial

This study is a randomized controlled phase II trial to evaluate the efficacy of the combination of stereotactic body radiation therapy (SBRT) and immunotherapy with postoperative chemotherapy in colorectal cancer liver metastasis (CRLM) patients with high risk of locally recurrence. Researchers will compare the combination therapy with the postoperative chemotherapy alone to see if postoperative chemotherapy plus SBRT and immunotherapy can further reduce the risk of recurrence and metastasis after surgery.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Liver Metastases; Radiotherapy; Immunotherapy
• Intervention / Treatment: Radiation: SBRT; Drug: Chemotherapy; Drug: PD-1 antibody

Detailed Description

40-50% of colorectal cancer patients have metastases at the time of diagnosis, of which liver metastases are the most common. Surgical resection is the most likely cure for CRLM patients, however, more than 50% of patients will experience recurrence within 2 years after resection of liver metastases. SBRT can be an effective and safe treatment modality, which can not only provide better local control of metastatic lesions, but also has a sensitizing immunotherapeutic effect. SBRT can effectively synergize with anti-PD-1/PD-L1 antibodies to activate the immune microenvironment of CRLM patients and improve survival. However, in CRLM patients after surgery, whether combining SBRT, immunotherapy and adjuvant chemotherapy results in better survival than chemotherapy alone, the evidence is insufficient.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fan Xia, M.D, PH.D; Phone Number: 13564676623 13564676623; Email: tcxiafan@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Xia Fan, M.D, PH.D; Phone Number: 13564676623; Email: tcxiafan@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. age ≥ 18 years old, female and male
2. pathological and imaging confirmed colorectal colorectal liver metastases (synchronous or heterochronous)
3. Metastatic liver lesions <= 5
4. Primary colorectal cancer under control
5. Absence of evidence of extra-hepatic diseases
6. Metastatic liver lesions received resection with insufficient margin (<0.5cm) or R1/R2 resection
7. Karnofsky >= 70
8. Adequate organ function without contraindications to surgery, radiotherapy and immunotherapy
9. Without previous antitumoral immunotherapy
10. With good compliance
11. Signed the inform consent

Exclusion Criteria:

1. Pregnancy or breast-feeding women
2. History of other malignancies within 5 years (except cured skin cancer and cervical cancer in situ)
3. History of uncontrolled epilepsy, central nervous system disease, or psychiatric disorders
4. Clinically serious heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmia requiring pharmacologic intervention, or history of myocardial infarction within the last 12 months
5. Immunodeficiency disease, autoimmune diseases or long-term using of immunosuppressive agents
6. Severe uncontrolled recurrent infections
7. Baseline blood and biochemical indicator do not meet the following criteria: neutrophils >=1.5×10^9/L, Hb >=90g/L, PLT >=100×10^9/L, ALT/AST<=2.5 ULN, Cr <= 1ULN
8. Allergic to any component of the therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: chemotherapy with radiotherapy and immunotherapy; radiotherapy: SBRT of liver lesions; postoperative chemotherapy and immunotherapy: chemotherapy by investigators' choice with sintilimab for 18 weeks	Radiation: SBRT; postoperative SBRT of liver lesions; Other Names: radiotherapy; Drug: Chemotherapy; XELOX/FOLFOX/FOLFIRI; Drug: PD-1 antibody; Sintilimab (200mg d1，q3w); Other Names: Sintilimab
Active Comparator: chemotherapy; postoperative chemotherapy: chemotherapy by investigators' choice for 18 weeks	Drug: Chemotherapy; XELOX/FOLFOX/FOLFIRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Evaluate the effect of the combination of adjuvant chemotherapy, SBRT and immunotherapy versus observation on progression free survival	From the date of randomization until the date of first documented progression or date of death from any cause, whichever come first, assessed up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local control rate	To evaluate local control rate after the combination of adjuvant chemotherapy, SBRT and immunotherapy in comparison to observation alone	From the date of randomization until the date of first documented locally tumor recurrence, assessed up to 12 months
Overall survival	To evaluate overall survival after the combination of adjuvant chemotherapy, SBRT and immunotherapy in comparison to observation alone	From date of randomization until the date of death from any cause, assessed up to 36 months
Grade 3-4 adverse effect rate	Rate of chemotherapy, SBRT and immunotherapy related adverse events	From date of randomization until the date of death from any cause, assessed up to 3 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Fan Xia, M.D,PH.D, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2023
• Primary Completion (Estimated): September 25, 2025
• Study Completion (Estimated): September 25, 2025

Study Registration Dates

• First Submitted: November 2, 2023
• First Submitted That Met QC Criteria: November 2, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Digestive System Neoplasms; Liver Diseases; Neoplastic Processes; Neoplasm Metastasis; Recurrence; Liver Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: FDRT-2023-258-3377

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No