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

Chinese Academy of Medical Sciences & Peking Union Medical College logo

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase

Not yet enrolling
Phase 3
Phase 2

Conditions

Radiotherapy
Rectal Neoplasms Malignant

Treatments

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

Study type

Interventional

Funder types

Other

Identifiers

NCT05484024
NCC22/206-3408

Details and patient eligibility

About

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.

Enrollment

588 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

588 participants in 2 patient groups

iTNT group
Experimental group
Description:
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.
Treatment:
Combination Product: CAPOX/mFOLFOX
Drug: Sintilimab
Radiation: Short-course radiotherapy
TNT group
Active Comparator group
Description:
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.
Treatment:
Combination Product: CAPOX/mFOLFOX
Radiation: Short-course radiotherapy

Trial contacts and locations

2

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Central trial contact

Wenjue Zhang; Yuan Tang

Data sourced from clinicaltrials.gov

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