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

Radiotherapy Clinical Trial

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05484024
• Other study ID #: NCC22/206-3408
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: August 6, 2022
• Est. completion date: July 31, 2030

Study information

• Verified date: July 2022
• Source: Chinese Academy of Medical Sciences
• Contact: Yuan Tang
• Phone: +86-15011304945
• Email: tangyuan82[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 588
• Est. completion date: July 31, 2030
• Est. primary completion date: July 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Radiotherapy
• Rectal Neoplasms
• Rectal Neoplasms Malignant

Intervention

Drug:
• Sintilimab
PD-1 inhibitor

Radiation:
• Short-course radiotherapy
Pelvic radiation

Combination Product:
• CAPOX/mFOLFOX
chemotherapy regimen

Locations

Country	Name	City	State
China	Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College	Beijing	Beijing
China	National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College	Shenzhen

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	complete remission	The rate of pathological complete remission plus clinical complete remission	one year
Primary	Disease-free survival rate		three year
Secondary	Incidence of acute toxicities during radiation, chemotherapy ± immunotherapy		three months
Secondary	Incidence of surgical complications		30 days
Secondary	Overall survival rate		three year
Secondary	Locoregional recurrence rate		three year
Secondary	Distance metastasis rate		three year
Secondary	Radical resection (R0)		one year
Secondary	Quality of life (QoL)	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.	From date of randomization until the date of death from any cause, assessed up to 10 years
Secondary	Quality of life (QoL)	Quality of life will be evaluated using EORTC QLQ-Cr29 (range 0-100). It evaluates the quality of life from 29 aspects, including defecation function, urine function,pain, sex function, etc. The higher scores mean a better quality of life.	From date of randomization until the date of death from any cause, assessed up to 10 years
Secondary	Quality of life (QoL)	Quality of life will be evaluated using Wexner score(range 0-20). It evaluates the defecation function. The lower scores mean a better quality of life.	From date of randomization until the date of death from any cause, assessed up to 10 years