Neoadjuvant Safety of Sintilimab + XELOX + Bevacizumab in PMMR/MSS CRLM Patients

NCT04940546 | Active Not Recruiting Phase 1

• 1 other identifier: neoSXB-MSS-CRLM
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, single arm study aims to evaluate the preoperative neoadjuvant safety of Sintilimab combined with XELOX plus bevacizumab in colorectal patients with liver metastasis and pMMR/MSS status.

Conditions

Colorectal Cancer Metastatic

Keywords

Colorectal liver metastasis; pMMR/MSS; Sintilimab; XELOX; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Adverse events

  Number of patients with adverse events and severity according to NCICTCAE v5.0 during treatment period and using Clavien-Dindo classification of surgical complications for surgery.

  up to 24 months

Secondary Outcomes (4)

• Pathological Remission Rate

  up to 24 months

• Objective Response Rate

  up to 24 months

• Recurrence Free Survival

  up to 24 months

• Overall Survival

  up to 24 months

Study Arms (1)

Sintilimab + XELOX + Bevacizumab

EXPERIMENTAL

Patients receive Sintilimab + XELOX regimen every 3 weeks for 4 cycles and Bevacizumab every 3 weeks for 2 cycles. Details are as follows: Sintilimab: 200mg intravenously, d1 Oxaliplatin: 135mg/m2 intravenously, d1 Capecitabine: 2g/m2 orally, d1-14 for Bevacizumab: 7.5mg/kg intravenously, d1 After neoadjuvant treatment, if there are no new lesions upon radiological and Multidisciplinary Team (MDT) assessment, radical surgery is performed within 6 weeks. If there are new lesions the surgical team will assess the optimal time for surgery. After surgery 4 cycles of XELOX regimen is advised for adjuvant therapy.

Drug: Sintilimab; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Bevacizumab

Interventions

Sintilimab DRUG

Mode of administration: Intravenously

Also known as: Anti-PD-1 monoclonal antibody IBI308

Sintilimab + XELOX + Bevacizumab

Oxaliplatin DRUG

Mode of administration: Intravenously

Also known as: Eloxatin

Sintilimab + XELOX + Bevacizumab

Capecitabine DRUG

Mode of administration: Orally

Also known as: Xeloda

Sintilimab + XELOX + Bevacizumab

Bevacizumab DRUG

Mode of administration: Intravenously

Also known as: Avastin

Sintilimab + XELOX + Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years old and ≤75 years old
• Histologically confirmed colorectal adenocarcinoma
• Radiologically and/or pathologically confirmed liver metastasis
• Immunohistochemistry and/or genetic testing confirmed pMMR/MSS
• Absence of extrahepatic metastasis confirmed by CT, MRI or PET/CT (if necessary)
• Primary lesion has been or can be removed by radical surgery
• Liver metastases can be resected (or using intraoperative radiofrequency) and is expected to achieve tumor-free status (NED) after surgery. Resectable liver metastases are defined explicitly as ① less than 5 metastatic lesions; ② R0 resection is achievable by resection or intraoperative radiofrequency; ③ Remaining liver volume is expected to be sufficient after surgery; ④ The following can be retained after resection: One hepatic vein, preserve blood flow in and out of the remaining liver, the bile duct, and at least 2 adjacent livers segments ⑤ There is no extrahepatic metastasis.
• Apart from surgical resection of the primary lesion, he/she has not received any anti-tumor treatment for liver metastasis (including chemotherapy, targeted drugs, interventional therapy, immunotherapy, radiotherapy, etc.)
• Normal hematological function (platelets\>90×109/L; white blood cells\>3×109/L; neutrophils\>1.5×109/L)
• Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), transaminase ≤ 5 times ULN, alkaline phosphatase ≤2.5 ULN, No ascites, normal coagulation function, albumin ≥35g/L
• Child-Pugh classification of the liver is A
• Serum creatinine is less than the upper limit of normal (ULN), or the calculated creatinine clearance rate is greater than 50ml/min (using Cockcroft-Gault formula)
• ECOG score 0-1
• Life expectancy\> 3 months
• Signed and written informed consent

You may not qualify if:

• Presence of distant metastases outside the liver after the diagnosis of colorectal cancer
• Liver metastases have been treated with chemotherapy, targeted drugs, intervention, immunotherapy, radiotherapy, etc.
• No surgical resection plan for liver metastases
• Received oxaliplatin-containing adjuvant chemotherapy in the past 1 year
• Any residual toxicity from previous chemotherapy (except for hair loss), such as peripheral neuropathy ≥NCI CTC v3.0 Grade 2
• Use of immunosuppressive drugs within 1 week before treatment, not including nasal sprays, inhalation or other local treatments, partial glucocorticoids or physiological doses of systemic glucocorticoids (i.e. not more than 10 mg/day prednisone or equivalent doses of other glucocorticoids) or use of corticoids to prevent contrast agent allergy
• Suffering from interstitial lung disease that requires steroid therapy
• Medical history of active autoimmune disease that needs symptomatic treatment within the past 2 years. Vitiligo, psoriasis, hair loss, or Grave's disease that do not require systemic treatment within the past 2 years, or hypothyroidism patients that only need thyroid hormone replacement therapy and type I diabetic patients requiring only insulin replacement therapy can be enrolled
• History of primary immunodeficiency
• Active tuberculosis
• Known history of allergies related to organ transplantation or hematopoietic stem cell transplantation
• Allergic to any monoclonal antibody or chemotherapeutic drug (fluorouracil, oxaliplatin) and its ingredients
• Have bleeding tendency or coagulopathy
• Patients with apparent symptoms of intestinal obstruction
• Hypertensive crisis or hypertensive encephalopathy

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Interventions

sintilimab; Oxaliplatin; Capecitabine; Bevacizumab

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: June 18, 2021
• First Posted: June 25, 2021
• Study Start: June 16, 2021
• Primary Completion: October 30, 2023
• Study Completion: October 30, 2025
• Last Updated: December 3, 2024

Record last verified: 2024-11

Locations

CN (1)