Radiotherapy, Rectal Neoplasms Malignant
Conditions
Keywords
rectal cancer, short-course radiotherapy, total neoadjuvant therapy, PD-1 inhibitor
Brief summary
This phase II/III trial studies how well neoadjuvant short-course radiotherapy and chemotherapy with or without PD-1 inhibitors works in treating patients with locally advanced rectal adenocarcinoma. Neoadjuvant short-course radiation therapy followed by two-drug regimen chemotherapy, such as CAPOX, were shown to be non-inferior to standard long-course chemoradiotherapy in our previous STELLAR study. Immune checkpoint inhibitors (ICIs) using monoclonal antibodies, such as PD-1 or PD-L1 inhibitor, show promising efficiency and reliable security in some limited sample prospective or retrospective studies. When treating patients with locally advanced rectal cancer, giving sequential neoadjuvant short-course radiotherapy and chemotherapy with PD-1 inhibitor may work better.
Interventions
DRUGSintilimab
PD-1 inhibitor
RADIATIONShort-course radiotherapy
Pelvic radiation
COMBINATION_PRODUCTCAPOX/mFOLFOX
chemotherapy regimen
Sponsors
Chinese Academy of Medical Sciences
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
* Biopsy proven rectal adenocarcinoma; * Distance between tumour and anal verge≤ 10cm; * Locally advanced tumour;(8th edition AJCC/UICC staging :cT3-T4N0/cT2-4N+，M0) Cancer Staging must be based on pelvic MRI or Endoscopic ultrasound; * Eastern Cooperative Oncology Group(ECOG) performance score ≤ 1; * Mentally and physically fit for chemotherapy; Adequate blood counts: White blood cell count ≥3.5 x 109/L Haemoglobin levels ≥100g/L Platelet count ≥100 x 109/L Creatinine levels ≤1.0× upper normal limit（UNL） Urea nitrogen levels ≤1.0× upper normal limit（UNL） Alanine aminotransferase(ALT) ≤1.5× upper normal limit（UNL） Aspartate aminotransferase(AST) ≤1.5× upper normal limit（UNL） Alkaline phosphatase(ALP) ≤1.5× upper normal limit（UNL） Total bilirubin(TBIL) ≤1.5× upper normal limit（UNL） * No excision of tumor, chemotherapy or other anti-tumor treatment after the diagnosis. * No previous pelvic radiation history； * Written informed consent;
Exclusion criteria
* Previous treatment with anti-PD-1/L1 and anti-CTLA-4 or other immune experimental drugs. * Severe autoimmune disease: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (e.g. Wegener's granulomatosis) * Symptomatic interstitial lung disease or active infectious/non-infectious pneumonia. * At risk for bowel perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer or other known risk factors for bowel perforation. * history of other malignancies, excluding curable non-melanotic skin cancer and cervix carcinoma in situ； * Active infection, heart failure, heart attack within 6 months, unstable angina or unstable arrhythmia. * Any condition investigator considered may interfere with the results or place the patient at increased risk of treatment complications, or other uncontrollable disease. * Pregnancy or breast feeding * Immunodeficiency disorders including human immunodeficiency virus (HIV), or history of organ transplantation, allogeneic stem cell transplantation * Active hepatitis B virus (HBV) hepatitis (HBV-DNA ≥ 2000 U/mL), hepatitis C virus (HCV) hepatitis, active tuberculosis infection. * Oncology vaccination history or any vaccination within 4 weeks prior to the start of treatment.(Note: influenza vaccines are mostly inactivated and therefore allowed, intranasal preparations are usually live attenuated vaccines and therefore not allowed) * Concomitant other immune agents, chemotherapeutic agents, other drugs in clinical studies, and long term cortisol application
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| complete remission | one year | The rate of pathological complete remission plus clinical complete remission |
| Disease-free survival rate | three year | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival rate | three year | — |
| Locoregional recurrence rate | three year | — |
| Incidence of acute toxicities during radiation, chemotherapy ± immunotherapy | three months | — |
| Radical resection (R0) | one year | — |
| Quality of life (QoL) | From date of randomization until the date of death from any cause, assessed up to 10 years | Quality of life will be evaluated using EORTC QLQ-C30 (range 0-100). It evaluates the quality of life from 30 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life. |
| Distance metastasis rate | three year | — |
| Incidence of surgical complications | 30 days | — |
Countries
China
Contacts
Primary ContactYuan Tang
Backup ContactWenjue Zhang
Outcome results
None listed