Rectal Cancer, Radiotherapy, Immunotherapy, Chemotherapy
Conditions
Brief summary
This is a prospective, single-arm, biomarker-stratified, multicenter phase 2 clinical trial. All enrolled patients first receive short-course radiotherapy (SCRT), followed by measurement of serum β-hydroxybutyrate (β-HB) levels to calculate the post-radiotherapy elevation rate. Patients are stratified into an β-HB-positive stratum (elevation significantly) and an β-HB-negative stratum (no elevation), then randomized 1:1 within each stratum to receive either perioperative chemotherapy plus PD-1 inhibitor or perioperative chemotherapy alone. The primary endpoint is the complete response (CR) rate, defined as the composite of pathological complete response (pCR) and clinical complete response (cCR). The study aims to evaluate the efficacy and safety of adding PD-1 inhibitor to perioperative chemotherapy in LARC, and to validate post-radiotherapy β-HB elevation as a predictive biomarker for immunotherapy benefit.
Interventions
RADIATIONShort-course radiotherapy
Eligible subjects will receive short-course radiotherapy (SCRT). One week after the end of treatment, subjects continued to receive neoadjuvant chemotherapy.
DRUGCapecitabine
1000mg/m2, bid, po, d1-14,q3w
DRUGOxaliplatin
130mg/m2, ivgtt, d1,q3w
PROCEDURETME surgery
The surgery was performed 1 week after the end of neoadjuvant therapy.
200 mg via intravenous infusion every 3 weeks (q3w) for 6 cycles, initiated 1 week after radiotherapy completion.
OTHERWatch & Wait strategy
The Watch \& Wait (W\&W) strategy is an organ-preserving clinical management approach for patients with locally advanced rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant therapy. In this strategy, definitive surgical resection (total mesorectal excision, TME) is withheld, and patients are instead managed with a standardized, intensive surveillance regimen to monitor for disease regrowth.
Sponsors
Tao Zhang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients or their family members agree to participate in the study and sign the informed consent form; 2. Age 18-75 years, male or female; 3. Histologically confirmed Locally Advanced rectal adenocarcinoma; 4. inferior margin ≤ 10 cm from the anal verge; 5. ECOG performance status score is 0-1; 6. Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc; 7. There was no operative contraindication; 8. Laboratory tests were required to meet the following requirements: white blood cell (WBC) ≥ 4×109/L; Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥90 g/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance rate ≥50 mL/min; International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 9. Urinary protein \< 2+ or 24-hour urinary protein excretion \< 1 g at baseline.
Exclusion criteria
1. Patients with non-pMMR LARC； 2. Subjects who have previously received any form of immunotherapy, including but not limited to immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any other treatment targeting tumor immunomodulatory mechanisms; 3. Presence of any concurrent disease, condition (including laboratory abnormality), history of substance abuse, or current evidence thereof, which, in the judgment of the Investigator, may compromise subject safety, interfere with the process of obtaining informed consent, affect subject compliance, or confound the safety assessment of the investigational product(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| complete response (CR) rate | an expected average of 12 months | Defined as pathological complete response (pCR) + Clinical complete response (cCR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3-year disease-Free Survival | an expected average of 3 years | The time from the first day of disease free (operation date) to local or distant recurrence, or the death event caused by any reason, whichever occurs first |
| Overall Survival | an expected average of 5 years | The time from the date of randomization to the death caused by any cause |
| Adverse events (AEs) were graded according to the NCI CTCAE version 5·0 | an expected average of 1.5 years | Adverse events and surgical safety |
Countries
China
Contacts
CONTACTZhenyu Lin
CONTACTTao Zhang
PRINCIPAL_INVESTIGATORZhenyu Lin
Huazhong University of Science and Technology Tongji Medical College Union Hospital
Outcome results
None listed