Colorectal Cancer Metastatic
Conditions
Brief summary
This is a non-randomized, open-label, single-center clinical trial to evaluate efficacy and safety of sintilimab plus bevacizumab and chemotherapy on treatment in patients with advanced no liver metastatic MSS/pMMR colorectal cancer
Detailed description
The regimen involves 3-week cycles with bevacizumab (7.5 mg/m2 on days 1) and fixed doses of sintilimab (200 mg on day 1) and chemotherapy. The primary endpoint is progression-free survival (PFS). Secondary endpoints are Objective response rate(ORR), Disease control rate(DCR), Overall survival(OS) and quality of life. Adverse events are monitored and graded according to the Common Terminology Criteria for Adverse Events version 4.0.
Interventions
DRUGGroup A
Sintilimab 200mg Bevacizumab 7.5mg/kg Oxaliplatin 130mg/m2 Capecitabine 1250mg/m2
DRUGGroup B
Sintilimab 200mg Bevacizumab 7.5mg/kg Irinotecan 150mg/m2 Capecitabine 1250mg/m2
Sponsors
Anhui Provincial Cancer Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Sign written informed consent before implementing any experimental procedures 2. Over 18 years old 3. Histologically confirmed as colorectal adenocarcinoma without liver metastasis 4. At least one measurable lesion (RECIST 1.1) 5. Satellite stable (MSS) or low instability (MSI-L) or normal expression of DNA mismatch repair genes (pMMR) 6. ECOG PS score is 0-1 7. Progress after initial treatment or standard first-line treatment 8. Have sufficient organ and bone marrow function 9. Expected to survive for more than 3 months 10. Participants must have normal hematological test results, including： * absolute neutrophil count (ANC) greater than 1.5 × 109/L * hemoglobin greater than 8 g/dL * platelet count greater than 80-100 × 109/L 11. Participants' prothrombin time (PT) must be less than 1.5 times the upper limit of normal values, and activated partial thromboplastin time (APTT) must be less than 1.5% of the upper limit of abnormal values 12. Participants must have normal laboratory test results, including：serum creatinine levels less than or equal to 1.5 times the upper limit of the normal reference range, or creatinine clearance rates greater than 50 ml/min 13. For participants without liver metastasis, their alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels must be less than or equal to 2.5 times the upper limit of the normal reference range, and their serum total bilirubin levels must be less than 1.5 times the upper limit of the normal reference range 14. For female subjects of childbearing age, a urine or serum pregnancy test with negative results should be conducted within 3 days prior to the first administration of the study drug (Day 1 of the first cycle) 15. If there is a risk of conception, all subjects must use contraceptive measures with an annual failure rate of less than 1% throughout the entire treatment period until 120 days after the last administration of the study drug 16. The subjects must agree to provide sufficient tumor tissue samples for PD-L1 expression detection
Exclusion criteria
1. Known presence of active central nervous system (CNS) metastases and/or cancerous meningitis 2. Microsatellite instability (MSI-H) or loss of expression of DNA mismatch repair genes (dMMR) 3. Currently participating in interventional clinical research treatment, or having received other research drugs or used research instruments for treatment within 4 weeks before the first administration 4. Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs that stimulate or synergistically inhibit T cell receptors 5. Within 2 years prior to the first administration, there has been an active autoimmune disease requiring systemic treatment 6. Imaging shows tumor invasion/infiltration into large blood vessels, or researchers or radiologists assess a tendency towards bleeding 7. Have undergone major surgical treatment within 4 weeks prior to the initial administration of the investigational drug (excluding surgery for biopsy purposes) or are expected to undergo major surgery during the study period 8. Severe unhealed wounds, ulcers, or fractures 9. Undertook minor surgeries within 48 hours prior to the first receipt of the study drug 10. Currently or recently (within 10 days prior to receiving the first dose of the study drug) using aspirin (\>325 mg/day) or other known nonsteroidal anti-inflammatory drugs that can inhibit platelet function for 10 consecutive days 11. Currently or recently (within 10 days prior to receiving the first dose of the study drug), using full dose oral or parenteral anticoagulants or thrombolytic agents for treatment for 10 consecutive days 12. There is a genetic tendency for bleeding or coagulation dysfunction, or a history of thrombosis 13. Known allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation 14. Individuals known to be allergic to the active ingredients of the study drug 15. Prior to commencing treatment, the individual has not fully recovered from any toxicity and/or complications caused by any intervention measures (i.e., ≤ grade 1 or baseline, excluding fatigue or hair loss) 16. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive) 17. Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number detected is greater than the upper limit of normal value in the laboratory of the research center) 18. Pregnant or lactating women 19. The presence of any serious or uncontrollable systemic disease 21\. Other situations that the researchers believe are not suitable for inclusion, or other potential risks that are not suitable for participation in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | through study completion, an average of 1 year | Progression free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | up to 24 weeks | Objective response rate |
| DOR | up to 24 weeks | Duration of response |
| DCR | up to 24 weeks | Disease control rate |
| OS | through study completion, an average of 2 year | Overall survival |
Countries
China
Contacts
Primary ContactWang Gang
Outcome results
None listed