Radiotherapy, Rectal Cancer, Total Neoadjuvant Therapy, Immunotherapy
Conditions
Brief summary
This study is a national multicenter, prospective randomized controlled Phase III clinical trial designed to investigate the potential therapeutic benefit of immunotherapy combined with total neoadjuvant therapy (TNT) and to compare the efficacy of different radiotherapy modalities followed by immunotherapy.
Detailed description
This study is a national multicenter, prospective randomized controlled phase III clinical trial, with the following objectives: 1. For patients with high-risk LARC, to determine whether the efficacy of TNT combined with immunotherapy is superior to that of the treatment mode of LCRT followed by TNT; 2. To compare the differences in efficacy and toxicity between long-course radiotherapy and short-course radiotherapy under the mode of TNT combined with immunotherapy. For precision management of patients with cCR post-neoadjuvant therapy, dynamic MRD monitoring was implemented, including baseline and follow-up testing for patients having tumors ≤5 cm from the anal verge.
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.
RADIATIONLong-course radiotherapy
Long-course radiotherapy (LCRT, 50.4 Gy administered in 28 fractions) will be delivered concurrently with oral capecitabine.
DRUGCapecitabine
1000mg/m2, bid, po, d1-14,q3w
DRUGOxaliplatin
130mg/m2, ivgtt, d1,q3w
DRUGHLX10
300mg, ivgtt, q3w
PROCEDURETME surgery
The surgery was performed 1 week after the end of neoadjuvant therapy.
DRUGHLX10 placebo
300mg, ivgtt, q3w
Sponsors
Tao Zhang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
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. Immunohistochemistry and/or genetic testing confirmed pMMR/MSS; 5. inferior margin ≤ 10 cm from the anal verge; 6. Pelvic MRI shows high risk \[meets one of the following conditions\]: • Clinical tumor (cT) staging cT4a or cT4b (according to AJCC 8th Edition) • Extramural vascular infiltration • Clinical lymph node (cN) staging cN2 (according to AJCC 8th Edition) • Mesenteric fascia is involved • Lateral lymph node enlargement 7. ECOG performance status score is 0-1; 8. Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc; 9. There was no operative contraindication; 10. 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; 11. Urinary protein \< 2+ or 24-hour urinary protein excretion \< 1 g at baseline.
Exclusion criteria
1. Patients with non-high-risk 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 event-Free Survival | an expected average of 3 years | The time from the start of treatment to the occurrence of any of the following events, which ever occurs first: tumor disease progression on imaging as assessed by RECIST 1.1; tumor recurrence, including local recurrence or distant recurrence, as assessed on imaging or tissue biopsy transfer; death from any cause. |
| 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, MD
CONTACTTao Zhang, MD
PRINCIPAL_INVESTIGATORZhenyu Lin, MD
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed