Mismatch repair-proficient and/or microsatellite-stable, surgically unresectable, high-risk/very high-risk locally advanced mid-to-low rectal cancer
Conditions
Interventions
Prospective interventional cohort:Sintilimab in combination with CAPOX
Sponsors
harbin medical university cancer hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18 to 70 years old, male or female. 2. Histologically or cytologically confirmed rectal cancer with measurable tumor lesions. 3. Middle or low rectal cancer confirmed by digital rectal examination or proctoscopy, with the lower margin of rectal tumor lesions within 10 cm from the anal dentate line. 4. Clinical stage of cT4, or positive extramural vascular invasion (EMVI+), or positive mesorectal fascia involvement (MRF+), or positive lateral pelvic lymph node metastasis (LPLN+), or N2 stage; any one condition met is acceptable. 5. Patients clinically evaluated as unresectable, or patients who cannot receive anus-preserving surgery and attach great importance to anal function. 6. Genetically confirmed microsatellite-stable (MS-S), or immunohistochemically confirmed proficient mismatch repair (pMMR). 7. ECOG performance status score: 0 or 1. 8. No peritoneal metastasis or other distant metastases. Note: Distant metastases shall be verified by CT or MRI scan. Bone scan shall be performed if bone metastasis is suspected; PET-CT or laparoscopy shall be conducted if peritoneal metastasis is suspected; brain CT or MRI shall be arranged if brain metastasis is suspected. 9. No prior chemotherapy or surgical treatment targeting rectal cancer. 10. Adequate function of major vital organs (blood products and cellular growth factors are not allowed during screening):1). Absolute neutrophil count >=1.5×10?/L; platelet count >=100×10?/L; hemoglobin >=9 g/dL; 2). Thyroid-stimulating hormone (TSH) <=1×ULN. If TSH is abnormal, T3 and T4 shall be tested simultaneously; subjects with normal T3 and T4 levels are eligible for enrollment; 3). Total bilirubin <=1.5×ULN; ALT and AST <=5×ULN; 4). Serum creatinine <=1.5×ULN. 11. Women of childbearing potential must have a negative ß-HCG pregnancy test before treatment initiation. Fertile women and fertile men who have sexual intercourse with fertile women must agree to use effective contraceptive measures continuously during treatment and for 6 months after administration of the last study treatment dose. 12. Subjects voluntarily participate in this study and sign the informed consent form.
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women, or fertile individuals who refuse to adopt contraceptive measures. 2. History of other malignant tumors within the past 5 years. 3. Patients who have undergone major surgery and have not recovered from the adverse effects of the surgery. 4. Uncontrolled symptomatic brain metastases, uncontrollable psychiatric disorders, or severe intellectual or cognitive dysfunction. 5. Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severely impaired pulmonary function. 6. Active, known or suspected autoimmune diseases. Subjects with hypothyroidism requiring only hormone replacement therapy, or skin disorders without the need for systemic treatment (such as vitiligo, psoriasis or alopecia) are eligible for enrollment. 7. Active hepatitis B or hepatitis C. Patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral load less than 1000 IU/mL are permitted to participate in the study, but full standardized antiviral therapy must be continued or initiated throughout the study period. 8. Congestive heart failure, refractory arrhythmia, myocardial infarction within 6 months, unstable angina pectoris, stroke or transient ischemic attack; or other conditions that render patients intolerant to surgery. 9. Severe active infections requiring intravenous antibiotic therapy occurring during the enrollment period. 10. Hypersensitivity to any investigational drugs. 11. Administration or planned administration of live vaccines within 30 days prior to sintilimab infusion. 12. Confirmed history of HIV infection. 13. Patients who are unable to comply with the study protocol or follow-up requirements. 14. Subjects deemed inappropriate for participation in this trial by the investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Response Rate (pCR + cCR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Local Recurrence (LR) Rate;Tumor Regression Grade (TRG);R0 Resection;Sphincter-Preservation Rate;Overall Survival (OS);Major Pathological Response (MPR) Rate;Safety:;Disease-Free Survival (DFS); | — |
Countries
China
Contacts
Public ContactYu Han
harbin medical university cancer hospital
Outcome results
None listed