Clinical trial NCT05171660: Combination With Sintilimab and XELOX+Bevacizumab as 1st Line Therapy in RAS-mutant Metastatic Colorectal Cancer
Official title: A Randomized, Open, Multicenter Phase III Clinical Trial of Combination of Sintilimab Injection (IBI308) and XELOX+Bevacizumab Compared With XELOX+Bevacizumab as 1st Line Therapy of RAS-Mutant Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Colorectal Cancer Stage IV
Keywords: Colorectal Cancer Stage IV,
RAS gene mutation
Microsatellite stable
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2021-12-29
Enrollment: 446
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Sintilimab (R\&D code: IBI308) is a recombinant human-derived IgG4 type PD-1 monoclonal antibody. PD-1 inhibitor combined with chemotherapy has synergistic effect to further enhance anti-tumor immunity. This study is a phase III clinical study of a three-week regimen of sintilimab combined with the XELOX+ bevacizumab for RAS-mutant metastatic colorectal cancer patients who had not received any treatment before. The purpose of this study is to explore the efficacy of sintilimab combined with XELOX + bevacizumab as first line therapy.


Eligibility criteria: Inclusion Criteria:

1. Male or female, age ≥ 18 years old, ≤ 75 years old
2. Metastatic colorectal adenocarcinoma confirmed by histology, metastases cannot be removed
3. RAS mutation, BRAF V600E wild type, and microsatellite stable
4. ECOG 0 to 1
5. Life expectancy is at least 12 weeks
6. Hematological examination absolute neutrophil count (ANC)\>1.5×109/L, hemoglobin\>8g/dL and platelet\>100×109/L (according to the normal value of clinical trial center)
7. Prothrombin time (PT) \< 1.5 times the upper limit of normal value and normal thromboplastin time (APTT) \< 1.5 times the upper limit of normal value
8. Laboratory examination, serum creatinine is less than or equal to 1.5 times the upper limit of the normal reference range (if serum creatinine is elevated, 24 hours of urine must be collected, except for 24 hours creatinine clearance \> 50ml/min)
9. When there is no liver metastasis, ALT or AST is less than or equal to 2.5 times the upper limit of the normal value reference range, serum total bilirubin is less than or equal to 1.5 times the upper limit of the normal value reference range; for patients with liver metastasis, ALT or AST is less than or equal to 5 times the upper limit of the normal value reference range, serum total bilirubin is less than or equal to 3 times the upper limit of the normal value reference range
10. Women of childbearing age must be willing to use adequate contraception during study drug treatment
11. Informed consent has been signed
12. According to the definition of RECIST 1.1, the investigator determined that the patient had a measurable disease. Tumor lesions located in previous radiotherapy areas are considered measurable if they demonstrate progression.

Exclusion Criteria:

1. Active autoimmune disease requiring systemic treatment occurred in the previous 2 years.
2. Diagnosed as immunodeficiency or experimental treatment is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose. After consultation with the sponsor, the use of a physiological dose of corticosteroids may be approved.
3. Adverse events caused by anti-tumor monoclonal antibodies (mAbs) within 4 weeks prior to study day 1 or drugs received 4 weeks prior to the study have not recovered.
4. Adverse events caused by chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1, or previously received drugs, have not recovered (ie, ≤1 or reached baseline levels).

   Other malignancies that are progressing or require active treatment are known. Except for basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical carcinoma in situ that have undergone radical treatment.
5. Active central nervous system (CNS) metastasis and/or cancerous meningitis are known to exist.
6. There are active infections that require systemic treatment.
7. It is possible to confuse the test results, the medical history or disease evidence, the treatment or laboratory value abnormalities that hinder the subject's full participation in the study, or the investigator believes that participating in the study is not in the best interests of the subject.
8. There are known mental or substance abuse disorders that may have an impact on compliance with test requirements.
9. Female subjects who are pregnant or lactating, or who are expected to be pregnant during the planned trial period (from 120 days after screening visits to 120 days after the last dose of study treatment, or 180 days after the last dose of study treatment), or Male subjects whose spouse is pregnant.
10. A history of infection with human immunodeficiency virus (HIV) (HIV 1/2 antibody) is known.
11. Active hepatitis B or C.
12. Live vaccines were vaccinated within 30 days of the start date of the study treatment plan.
13. RAS wild type

Primary outcomes:
measure: Progression free survival time
timeFrame: From randomization to the first documented disease progression, or to death from any cause, up to 2 years
Secondary outcomes:
measure: Objective Response Rate
timeFrame: From randomization to disease progression
measure: Overall survival time
timeFrame: From randomization to death from any cause, up to 3 years
measure: Disease control rate
timeFrame: From randomization to disease progression
measure: Clinical benefit rate
timeFrame: From randomization to disease progression
measure: Adverse Events
timeFrame: From randomization to 28 days after disease progression
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Xuefeng Fang
state: Zhejiang
Study officials:
affiliation: 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
name: Ying Yuan
role: PRINCIPAL_INVESTIGATOR
References: