Sintilimab (IBI308) Combined With Bevacizumab + XELOX Regimen in Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

Official title:

Evaluation on the Tolerance and Preliminary Efficacy of Sintilimab (IBI308) Combined With Bevacizumab, Oxaliplatin and Capecitabine Regimen for Ras Gene Mutant and Microsatellite Stable Unresectable Metastatic Colorectal Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04194359
• Other study ID #: 2020-552
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 4, 2021
• Est. completion date: December 12, 2023

Study information

• Verified date: March 2023
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase II clinical study of Sintilimab (IBI308) combined with Bevacizumab, Oxaliplatin and Capecitabine regimen as first-line treatment in patients with RAS-mutant and microsatellite stable metastatic colorectal cancer. A total of 25 patients are planned to be enrolled.

Description:

This study is a phase II clinical study of Sintilimab (IBI308) combined with bevacizumab + XELOX regimen as first-line treatment in patients with RAS-mutant and microsatellite stable metastatic colorectal cancer. The study treatment took 21 days as a treatment cycle. Sintilimab (IBI308), bevacizumab and oxaliplatin were given intravenously on the first day of each cycle, and capecitabine was given from the first day to the 14th day. All adverse events will be graded according to NCI CTCAE (version 5.0). Up to 8 courses of inductive therapy would be given. During the treatment, CT was rechecked every 2 courses to evaluate the curative effect. Patients with objective response or stable disease (SD) would continue to receive sintilimab plus bevacizumab and oral capecitabine in each 21-day cycle as maintenance therapy until the confirmation of disease progression, death, unacceptable toxicity, or withdrawal of consent. A total of 25 patients are planned to be enrolled. When the number of subjects reaches 25 respectively, the enrollment ends to inquire about the safety and efficacy of Sintilimab (IBI308) combined with bevacizumab + XELOX.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: December 12, 2023
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female, age = 18 years old, = 75 years old;

2. Metastatic colorectal adenocarcinoma confirmed by histology and unresectable metastatic colorectal cancer confirmed by a multidisciplinary team;

3. RAS gene mutation, BRAF wild-type and microsatellite stable confirmed by polymerase chain reaction using a panel of six mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24, NR-27, and MONO-27);

4. ECOG performance status of 0-1;

5. Life expectancy=3 months;

6. Adequate organ and bone marrow functions: absolute neutrophil count >1.5×109/L, hemoglobin >8 g/dL, platelet count >100×109/L, prothrombin time <1.5 upper limit of normal (ULN), activated partial thromboplastin time <1.5 ULN, bilirubin =1.5×ULN (could be extended to 3×ULN in case of liver metastasis), blood aspartate aminotransferase and alanine aminotransferase =2.5×ULN (could be extended to 5×ULN in case of liver metastasis), serum creatinine level =1.5×ULN or creatinine clearance =50 mL/min, urinary protein / creatinine ratio < 1 (or urine analysis < 1 + or 24-hour urinary protein < 1g / 24 h;

7. Informed consent has been signed;

8. The presence of at least one measurable lesion assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;

Exclusion Criteria:

1. received previous treatment with any anti-programmed cell death protein 1 (PD-1) or anti-PD-L1 antibody;

2. received treatment with corticosteroids or other immunosuppressive agents within 14 days prior to study drug administration;

3. presence of autoimmune disease, known interstitial lung disease;

4. those with previous or concurrent malignancies expect for basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical carcinoma in situ that have undergone radical treatment.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer
• Microsatellite Stable
• RAS Mutation

Intervention

Drug:
• Sintilimab (IBI308)+bevacizumab+oxaliplatin+capecitabine
Humanized PD-1 antibody (Sintilimab, IBI308)+bevacizumab+oxaliplatin+capecitabine

Locations

Country	Name	City	State
China	the Second Affiliated Hospital of Medical College of Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	Objective Response Rate was defined as the proportion of patients with a best objective response of complete response (CR) or partial response (PR) according to RECIST criteria (version 1.1).	From Baseline to disease progress, up to 18 months
Primary	Adverse Events and Serious Adverse Events	Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0.	From Baseline to primary completion date, about 2 years
Secondary	Disease Control Rate	Disease Control Rate was defined as the proportion of patients with CR, PR, or SD according to RECIST criteria (version 1.1)	From Baseline to disease progress, up to 18 months
Secondary	Progression free survival	Progression-free survival is defined as the time from enrollment to the first documented disease progression according to RECIST version 1.1, or to death from any cause, whichever occurred first.	From Baseline to primary completion date, about 2 years