Short-course Radiotherapy Followed by Chemotherapy and PD-1 Inhibitor for Locally Advanced Rectal Cancer

Официальное название

Preoperative Short-course Radiotherapy Followed by Chemotherapy With or Without PD-1 Inhibitor for Locally Advanced Rectal Cancer: a Prospective, Multicenter, Randomized Controlled, Phase II/III Study (STELLAR II Study)

Обзор

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.

Вмешательства

• Препарат Sintilimab
  PD-1 inhibitor
• Лучевая терапия Short-course radiotherapy
  Pelvic radiation
• Комбинированный продукт CAPOX/mFOLFOX
  chemotherapy regimen

Первичные конечные точки

• complete remission [Срок оценки: one year]
• Disease-free survival rate [Срок оценки: three year]

Вторичные конечные точки (9)

• Incidence of acute toxicities during radiation, chemotherapy ± immunotherapy [Срок оценки: three months]
• Incidence of surgical complications [Срок оценки: 30 days]
• Overall survival rate [Срок оценки: three year]
• Locoregional recurrence rate [Срок оценки: three year]
• Distance metastasis rate [Срок оценки: three year]
• Radical resection (R0) [Срок оценки: one year]
• Quality of life (QoL) [Срок оценки: From date of randomization until the date of death from any cause, assessed up to 10 years]
• Quality of life (QoL) [Срок оценки: From date of randomization until the date of death from any cause, assessed up to 10 years]
• Quality of life (QoL) [Срок оценки: From date of randomization until the date of death from any cause, assessed up to 10 years]

Критерии участия

Критерии включения

• 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;

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College — Пекин
• National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shen — Шэньчжэнь

Публикации

• Tang Y, Li HY, Wei LC, Li N, Zhang WJ, Lu YF, Deng FY, Xu TZ, Shuai JC, Lei ZF, Meng XY, Qi SN, Song YW, Zhang WW, Jing H, Li G, Liu SX, Wang YJ, Liu Z, Ma HY, Wang NY, Chen B, Wang SL, Li YX, Zhao LN, Tang JQ, Jiang Z, Chen YG, Zhou HT, Hu C, Jin J. Short-course-based TNT with or without PD-1 inhibitor for pMMR locally advanced rectal cancer: Phase 2 results of a randomized trial (STELLAR II). Me PMID 40845854
• Zhang W, Tang Y, Wei L, Liu S, Wang W, Chi Y, Wang Y, Kang W, Huang W, Deng F, Li H, Ma H, Jiang L, Ding Z, Feng L, Li Y, Chen Y, Zhou H, Hu C, Jin J. Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: A study protocol of a randomized phase II/III trial (STELLAR II study). Colorectal Dis. 2024 Sep;26(9):1732-1740. d PMID 39020518

Идентификаторы

NCT: NCT05484024 · NCC22/206-3408

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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