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

NCT05484024 | Not Yet Recruiting Phase 2

• 1 other identifier: NCC22/206-3408
• Study Type: interventional
• Target: 588
• Locations: 1 country
• Sites: 2

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.

Conditions

Rectal Neoplasms Malignant; Radiotherapy

Keywords

rectal cancer; short-course radiotherapy; total neoadjuvant therapy; PD-1 inhibitor

Outcome Measures

Primary Outcomes (2)

• complete remission

  The rate of pathological complete remission plus clinical complete remission

  one year

• Disease-free survival rate

  three year

Secondary Outcomes (9)

• Incidence of acute toxicities during radiation, chemotherapy ± immunotherapy

  three months

• Incidence of surgical complications

  30 days

• Overall survival rate

  three year

• Locoregional recurrence rate

  three year

• Distance metastasis rate

  three year

Study Arms (2)

iTNT group

EXPERIMENTAL

The intervention of iTNT group is Short-course radiotherapy followed by neoadjuvant chemotherapy and PD-1 inhibitor, which consists of a short-course radiotherapy(SCRT, 5 Gy x 5 alone), then after 14 days of radiotherapy completed, four cycles of PD-1 inhibitor and four cycles of CAPOX or six cycles of mFOLFOX will be performed. The regimen of PD-1 inhibitor and CAPOX treatment includes Sintilimab 200 mg IV, day 1，Oxaliplatin 130 mg/m2 IV day 1，Capecitabine 1000 mg/m2 twice daily PO for 14 days(3 weeks per cycle). The regimen of PD-1 inhibitor and mFOLFOX treatment includes Sintilimab 200 mg IV day 1(3 weeks per cycle), Oxaliplatin 85 mg/m2 IV day 1, Leucovorin 400 mg/m2 IV day 1, 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion(2 weeks per cycle), then followed by a total mesorectal excision(TME) or Watch \& Wait strategy for clinical complete remission voluntary patients.

Drug: Sintilimab; Radiation: Short-course radiotherapy; Combination Product: CAPOX/mFOLFOX

TNT group

ACTIVE COMPARATOR

The intervention of TNT group is Short-course radiotherapy followed by neoadjuvant chemotherapy, which consists of a short-course radiotherapy(SCRT, 5 Gy x 5 alone), then after 14 days of radiotherapy completed, four cycles of CAPOX or six cycles of mFOLFOX will be performed. The regimen of CAPOX treatment includes Oxaliplatin 130 mg/m2 IV day 1，Capecitabine 1000 mg/m2 twice daily PO for 14 days(3 weeks per cycle). The regimen of mFOLFOX treatment includes, Oxaliplatin 85 mg/m2 IV day 1, Leucovorin 400 mg/m2 IV day 1, 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion(2 weeks per cycle), then followed by a total mesorectal excision(TME) or Watch \& Wait strategy for clinical complete remission voluntary patients.

Radiation: Short-course radiotherapy; Combination Product: CAPOX/mFOLFOX

Interventions

Sintilimab DRUG

PD-1 inhibitor

Also known as: Immune checkpoint inhibitor

iTNT group

Short-course radiotherapy RADIATION

Pelvic radiation

Also known as: hypofraction

TNT group; iTNT group

CAPOX/mFOLFOX COMBINATION_PRODUCT

chemotherapy regimen

Also known as: neoadjuvant chemotherapy

TNT group; iTNT group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese Academy of Medical Sciences: lead

Study Sites (2)

Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College

Beijing, Beijing Municipality, China

Location

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Shenzhen, China

Location

Related Publications (2)

• 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). Med. 2025 Nov 14;6(11):100807. doi: 10.1016/j.medj.2025.100807. Epub 2025 Aug 21.

  PMID: 40845854 DERIVED

• 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. doi: 10.1111/codi.17090. Epub 2024 Jul 17.

  PMID: 39020518 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

sintilimab; Immune Checkpoint Inhibitors; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Combined Modality Therapy; Therapeutics

Central Study Contacts

Yuan Tang

CONTACT

+86-15011304945; tangyuan82@126.com

Wenjue Zhang

CONTACT

+86-13620986880; wenjuezhang@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 21, 2022
• First Posted: August 2, 2022
• Study Start: August 6, 2022
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2030
• Last Updated: August 2, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)