Clinical trial NCT05484024: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Rectal Neoplasms Malignant
Radiotherapy
Keywords: rectal cancer
short-course radiotherapy
total neoadjuvant therapy
PD-1 inhibitor
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
First posted: 2022-08-02
Enrollment: 588
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: complete remission
timeFrame: one year
measure: Disease-free survival rate
timeFrame: three year
Secondary outcomes:
measure: Incidence of acute toxicities during radiation, chemotherapy ± immunotherapy
timeFrame: three months
measure: Incidence of surgical complications
timeFrame: 30 days
measure: Overall survival rate
timeFrame: three year
measure: Locoregional recurrence rate
timeFrame: three year
measure: Distance metastasis rate
timeFrame: three year
measure: Radical resection (R0)
timeFrame: one year
measure: Quality of life (QoL)
timeFrame: From date of randomization until the date of death from any cause, assessed up to 10 years
measure: Quality of life (QoL)
timeFrame: From date of randomization until the date of death from any cause, assessed up to 10 years
measure: Quality of life (QoL)
timeFrame: From date of randomization until the date of death from any cause, assessed up to 10 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College
state: Beijing
city: Shenzhen
country: China
facility: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Study officials:
References: