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To evaluate the efficacy and safety of short-course radiotherapy followed by CAPOX and carrilizumab and bevacizumab or cetuximab in the initial treatment of unresectable metastatic rectal cancer
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Can't remove RAS/BRAF completely wild | Experimental | CAPOX+ Camrelizumab + Cetuximab |
|
| RAS/BRAF mutations cannot be resected | Experimental | CAPOX+ Camrelizumab + Bevacizumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAPOX+ Camrelizumab+ Cetuximab | Drug | For advanced primary treatment of unresectable rectal cancer, primary radiation therapy DT 25Gy/5F, and rest for 1 week, followed by CAPOX chemotherapy + Camrelizumab + Bevacizumab or Cetuximab (KRAS, NRAS, and BRAF all wild-type Cetuximab, KRAS, NRAS, and BRAF variants selected Bevacizumab) for 4-6 months, after which Capecitabine + Camrelizumab + Bevacizumab or Cetuximab was maintained |
| Measure | Description | Time Frame |
|---|---|---|
| ORR | Objective response rate | From enrollment to initial efficacy evaluation,assessed up to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| PFS | Progression free survival | From enrollment to the first appearance of disease progression or date of deathfrom any cause,whichever came first, assessed up to 18 months |
| OS | Overall Survival |
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Inclusion Criteria:
Sign a written informed consent and be able to comply with the visiting arrangements and related procedures stipulated in the programme;
Age ≥18 years old and ≤75 years old, gender is not limited;
Histologically confirmed rectal cancer with initial treatment (no surgery, radiotherapy, chemotherapy, targeted therapy or immunotherapy);
Radiologically confirmed unresectable metastatic rectal cancer (cTxNxM1);
Tissue samples must be provided for molecular typing (such as PD-L1, MSI, KRAS, NRAS, BRAVF, etc.), and newly acquired groups are preferred For patients who cannot provide newly obtained tissue, 5-8 paraffin sections with a thickness of 5um can be provided for archiving.
No serious abnormality of blood system, heart, lung, liver, kidney function and immune deficiency;
Baseline * (within 7 days before the first administration of the study drug) blood routine tests meet the following requirements:
Hemoglobin ≥90g/L Absolute neutrophil count (ANC) ≥1.5×109
/L Platelet count ≥100×109/L Eosinophils ≤1.5× Upper limit of normal (ULN)
* Throughout the protocol, "baseline" is defined as the last available observation before the first administration of the investigational drug. Subjects must not have received blood transfusion products (including red suspension, apheresis platelets, cryoprecipitate, etc.), erythropoietin, or colony-stimulating factor support therapy within 7 days prior to blood sample collection.
Serum biochemical tests at baseline (within 7 days before the first dose) met the following requirements
Requirements:
Total bilirubin ≤1.5× Upper limit of normal (ULN) (if total bilirubin > 1.5× upper limit of normal, combined with bilirubin
≤ULN was allowed to be included in the study); Aspartate aminotransferase (AST) or Alanine aminotransferase (AST) ALT) ≤2.5× upper limit of normal value; Serum Creatinine ≤1.5×ULN or Clearance of Creatinine (CCr) ≥45mL/min were obtained by Cockcroft-Gault formula Calculate CCr (using actual body weight); Albumin ≥30g/L.
Coagulation tests at baseline (within 7 days before the first dose) meet the following requirements:
International normalizaed ratio (INR) ≤1.5×ULN (≤3× if receiving steady dose anticoagulation therapy) ULN); Partial thromboplastin time (PTT) (or activated partial plastin time (PTT)) thromboplastin time, aPTT]) ≤1.5×ULN (≤3×ULN if receiving stable dose anticoagulant therapy);
Urine routine examination at baseline (within 7 days before the first dose) meets the following requirements: urinary protein (UPRO) < 2+ or 24-hour urinary protein quantity < 1g;
At least one measurable lesion according to RECIST v1.1 (Solid tumor) criteria;
The Physical status score (ECOG PS) of the Eastern United States Tumor Consortium was 0 or 1;
Expected survival time ≥3 months.
Female subjects of childbearing age or male subjects whose partner is a female of childbearing age agree to strictly use effective contraception throughout the treatment period and for 6 months after the treatment period
Exclusion Criteria:
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|
| CAPOX+ Camrelizumab+ Bevacizumab | Drug | For advanced primary treatment of unresectable rectal cancer, primary radiation therapy DT 25Gy/5F, and rest for 1 week, followed by CAPOX chemotherapy + Camrelizumab + Bevacizumab or Cetuximab (KRAS, NRAS, and BRAF all wild-type Cetuximab, KRAS, NRAS, and BRAF variants selected Bevacizumab) for 4-6 months, after which Capecitabine + Camrelizumab + Bevacizumab or Cetuximab was maintained |
|
| From enrollment to patient death,assessed up to 36 months |
| DCR | Disease Control Rate | Through out the study (24 months) |
| Adverse Event (AE), Treatment-Emergent AE (TEAE), Adverse Event of SpecialInterest (AESl) and Serious Adverse Event (SAE) | Adverse events will be assessed by investigator(s) according to CommonTerminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0). | Through out the study (up to 36 months) |