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

Official title

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)

Overview

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

• Drug Sintilimab
  PD-1 inhibitor
• Radiation Short-course radiotherapy
  Pelvic radiation
• Combination product CAPOX/mFOLFOX
  chemotherapy regimen

Primary outcome measures

• complete remission [Time frame: one year]
• Disease-free survival rate [Time frame: three year]

Secondary outcome measures (9)

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

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

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

Publications

• 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

Identifiers

NCT: NCT05484024 · NCC22/206-3408

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗