Clinical trial NCT04194359: Sintilimab (IBI308) Combined With Bevacizumab + XELOX Regimen in Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
RAS Mutation
Microsatellite Stable
Keywords: RAS-mutant Metastatic Colorectal Cancer
Immunotherapy
Anti-PD-1
Checkpoint
Efficacy
Safety
Microsatellite stable
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2019-12-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: From Baseline to disease progress, up to 18 months
measure: Adverse Events and Serious Adverse Events
timeFrame: From Baseline to primary completion date, about 2 years
Secondary outcomes:
measure: Disease Control Rate
timeFrame: From Baseline to disease progress, up to 18 months
measure: Progression free survival
timeFrame: From Baseline to primary completion date, about 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: the Second Affiliated Hospital of Medical College of Zhejiang University
state: Zhejiang
Study officials:
affiliation: The Second Affiliated Hospital of Medical College of Zhejiang University
name: Ying Yuan, MD
role: STUDY_CHAIR
References: