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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Colorectal Cancer; Microsatellite Stable; RAS Mutation
• Intervention / Treatment: Drug: Sintilimab (IBI308)+bevacizumab+oxaliplatin+capecitabine

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The Second Affiliated Hospital of Medical College of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sintilimab (IBI308) plus Bevacizumab, Oxaliplatin and Capecitabine; Sintilimab (IBI308)：200MG, once every three weeks; Bevacizumab:7.5mg/kg, once every three weeks; oxplatin: 135 mg per square meter body surface, once every three weeks; Capecitabine : Capecitabine 1 gram per square meter body surface area, from the first day to the 14th day	Drug: Sintilimab (IBI308)+bevacizumab+oxaliplatin+capecitabine; Humanized PD-1 antibody (Sintilimab, IBI308)+bevacizumab+oxaliplatin+capecitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: Ying Yuan, MD, The Second Affiliated Hospital of Medical College of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Actual): November 30, 2022
• Study Completion (Anticipated): December 12, 2023

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Immunotherapy; Anti-PD-1; Microsatellite stable; Checkpoint; RAS-mutant Metastatic Colorectal Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: 2020-552

Drug and device information, study documents

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