Locally Advanced Rectal Cancer
Conditions
Brief summary
The purpose of this study is to explore the efficacy and safety of involved-field radiotherapy-TNT combined with PD-1 inhibitors in pMMR locally advanced rectal cancer.
Interventions
DRUGCapecitabine
Capecitabine: 825mg/m2, bid;
DRUGCamrelizumab
Camrelizumab: 200mg
DRUGCAPOX
CAPOX
RADIATIONInvolve-field irradiation
Involve-field irradiation: Primary rectal tumor + metastatic or suspicious pelvic lymph nodes, mesorectal region, and presacral region
RADIATIONElective nodal irradiation
Elective nodal irradiation: Large pelvic field
PROCEDURETME surgery
TME surgery
Sponsors
Hebei Medical University Fourth Hospital
Study design
Allocation
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. Age ≥18 years old, male or female; 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; 3. Pathologic diagnosis of adenocarcinoma of the rectum, definite pMMR type; 4. Clinical staging of T3-4NanyM0 or T1-2N+M0 (based on AJCC 8th edition staging criteria); 5. The lower margin of the primary tumor is located below the peritoneal reflex or the lower margin of the tumor is ≤10 cm from the anal verge; 6. Pre-enrollment laboratory indicators meet the following indicator ranges： 1)Blood: absolute neutrophils ≥1.5×10\^9/L, platelets ≥100×10\^9/L, hemoglobin ≥90g/L; 2)Liver and kidney function: ALT/AST ≤ 2.5 x ULN, total bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60mL/min (Cockcroft-Gault formula)； 3)Coagulation: INR ≤ 1.5, APTT ≤ 1.5 x ULN (for those not receiving anticoagulation)； 7. Women or men of childbearing potential need to agree to use effective contraception during the study and for 6 months after the last treatment session; 8. Voluntary written informed consent and commitment to complete the full treatment and follow-up program.
Exclusion criteria
1. Pathologic type is other specific types such as neuroendocrine carcinoma, squamous carcinoma, etc; 2. Previous radiotherapy, chemotherapy, targeted or immunotherapy for rectal cancer; 3. Active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis requiring long-term immunosuppressive therapy)； 4. Presence of active infection (e.g. HIV, HBV/HCV viral load positive requiring stabilization on antiretroviral therapy)； 5. Severe cardiovascular disease (e.g., myocardial infarction within 6 months, unstable angina, uncontrolled hypertension \>160/100 mmHg)； 6. History of other malignant tumors (except non-melanoma skin cancers, cervical cancer in situ, etc. cured for ≥5 years)； 7. Uncontrolled diabetes mellitus (HbA1c \> 8%), abnormal thyroid function (TSH outside normal range and requiring pharmacologic intervention)； 8. Severe chronic bowel disease (e.g., Crohn's disease, active ulcerative colitis)； Patients deemed by the investigator to be unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CR rate | within 5 weeks | CR defined as patient achieving pCR and cCR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R0-resection rate | within 3 weeks after surgery | R0-resection defined as patients without tumor cell infiltration in the tissue 1mm from the resection margin |
| Preservation rate of adjacent invaded organs | within 3 weeks after surgery | The involved organs were successfully preserved during the operation |
| ORR | within 5 weeks | Defined as the percentage of complete response (CR) and partial response (PR) to tumor volume reduction according to RECIST v1.1 criteria |
| MPR rate | within 3 weeks after surgery | MPR defined as patients achieving a major pathological response after surgery. |
| 3-year OS | 3 years | OS defined as time from randomization to death from any cause. |
| Incidence of adverse reactions | 1 year | Occurrence of adverse reactions during therapy |
| 3-year Event Free Survival | 3 years | EFS defined as time from randomization to objectively observed tumor progression (local recurrence, new disease, or distant metastasis), development of a second malignancy, or death (death from any cause). |
Countries
China
Contacts
Primary ContactFengpeng Wu, Professor
Outcome results
None listed