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

Colorectal Cancer Clinical Trial

— IMPROVE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06120127
• Other study ID #: FDRT-2023-258-3377
• Status: Recruiting
• Phase: Phase 2
• Start date: September 25, 2023
• Est. completion date: September 25, 2025

Study information

• Verified date: November 2023
• Source: Fudan University
• Contact: Fan Xia, M.D, PH.D
• Phone: 13564676623
• Email: tcxiafan[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 25, 2025
• Est. primary completion date: September 25, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Immunotherapy
• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis
• Radiotherapy
• Recurrence

Intervention

Radiation:
• SBRT
postoperative SBRT of liver lesions

Drug:
• Chemotherapy
XELOX/FOLFOX/FOLFIRI
• PD-1 antibody
Sintilimab (200mg d1,q3w)

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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