Neoadjuvant Short-course Radiotherapy Followed by the Combination of Immunotherapy and Chemotherapy in Locally Advanced Rectal Cancer

NCT04663763 | Unknown Phase 2

• 1 other identifier: IRB-2020-336
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open-label, prospective phase II clinical trial to evaluate the combination of neoadjuvant short-course radiotherapy and immunotherapy (PD-1 antibody) for patients with locally advanced rectal cancer (LARC). A total of 40 patients will be enrolled in this trial to receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody. Then they will receive the TME surgery and another 4 cycles of CAPOX chemotherapy. There are two cohorts according to the microsatellite instability status: (1) the micro-satellite stable (MSS) cohort（n=32), (2) the MSI-high cohort (n=8). The primary end point is the rate of pathological complete response (pCR). The long-term prognosis and adverse effects will also be evaluated and analyzed.

Conditions

Locally Advanced Rectal Cancer

Keywords

Neoadjuvant short-course radiotherapy; Immunotherapy; Locally advanced rectal cancer; Pathological complete response

Outcome Measures

Primary Outcomes (1)

• pCR rate

  Pathologic complete response rate

  The TME surgery will be recommended at 1 week after the neoadjuvant therapy. The pCR rate is evaluated after surgery. Assessed up to 6 months

Secondary Outcomes (6)

• 3-year DFS

  Assessed up to 3 years

• 3-year local recurrence rate

  Assessed up to 3 years

• 3-year OS

  Assessed up to 3 years

• Grade 3-4 adverse effects rate

  Assessed up to 3 years

• Surgical complications

  Assessed up to 3 years from the TME surgery

Study Arms (1)

Neoadjuvant short-course radiotherapy+immunotherapy+chemotherapy

EXPERIMENTAL

A total of 40 patients receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody, finally receive the TME surgery and another 4 cycles of CAPOX chemotherapy. Interventions: Shor-course radiotherapy: 25Gy/5Fx; Induction immunotherapy: Sintilimab 200mg ivgtt d1 q3w x 4 cycles; Concurrent Chemotherapy: Oxaliplatin: 130mg/m2 d1 q3w + Capecitabine: 1000mg/m2 d1-14 q3w x 4 cycles;

Drug: PD-1 antibody; Drug: Capecitabine; Drug: Oxaliplatin

Interventions

PD-1 antibody DRUG

Sintilimab is a humanized IgG4 monoclonal antibody against the programmed death-1 (PD-1) receptor. Usage: 200mg ivgtt d1 q3w.

Also known as: Sintilimab

Neoadjuvant short-course radiotherapy+immunotherapy+chemotherapy

Capecitabine DRUG

Usage: 1000mg/m2 d1-14 q3w

Neoadjuvant short-course radiotherapy+immunotherapy+chemotherapy

Oxaliplatin DRUG

Usage: 130mg/m2 d1 q3w

Neoadjuvant short-course radiotherapy+immunotherapy+chemotherapy

Eligibility Criteria

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

You may qualify if:

• \. Pathological confirmed rectal adenocarcinoma and the distance from anal verge less than 12 cm;
• \. Clinical stage T3-4 and/or N+ (AJCC 8th);
• \. No distant metastases;
• \. Age 18-70 years old, female and male;
• \. ECOG 0-1;
• \. No previous chemotherapy, radiotherapy, immunotherapy or other anti-tumor treatment;
• \. Adequate organ function defined at baseline as:
• ANC ≥1.5×109 /L，PLt ≥75×109 /L，Hb ≥90 g/L;
• TBIL ≤1.5×ULN, ALT ≤2.5ULN, AST ≤2.5ULN, BUN and Cr ≤1×ULN or Ccr ≥50ml/min (Cockcroft-Gault formula);
• INR ≤1.5×ULN or PT ≤1.5×ULN (If the patient is receiving anticoagulant therapy, PT should be within the intended use range of the anticoagulant drug);
• \. With good compliance and no serious comorbidity;
• \. Women of childbearing age must have taken reliable contraceptive measures or have a pregnancy test (serum or urine) within 7 days prior to enrollment and the results are negative;
• \. Subject volunteers to join the study, sign the informed consent.

You may not qualify if:

• \. History of other uncured malignancies within 5 years. Cured tumor with good prognosis, such as skin basal cell carcinoma, cervical cancer and superficial bladder cancer, will be excluded;
• \. Have received surgery within 4 weeks before the enrollment;
• \. History of obstruction within 6 months before the enrollment;
• \. History of active autoimmune disease, interstitial lung disease, epilepsy and dysphrenia;
• \. With uncontrolled cardiovascular disease: active coronary heart disease; grade III-IV cardiac insufficiency according to the NYHA criteria; and myocardial infarction within 1 year;
• \. With active infection or fever of \>38.5 ℃ with unknown cause (tumor-induced fever judged could be enrolled);
• \. DPD deficiency;
• \. Allergic to any component of chemotherapy or immunotherapy;
• \. With congenital or acquired immunodeficiency (such as those with HIV infection), active hepatitis B or hepatitis C;
• \. Usage of corticosteroids (prednison dose of \> 10 mg/day) or other immunosuppressors for systemic treatment within the first 14 days of research;
• \. Receive attenuated live vaccine within 4 weeks before the research;
• \. Pregnant women or breast-feeding women;
• \. With other factors that would force to terminate the clinical trial ahead of time, such as the development of other severe comorbidity that required combined treatment, and family or social factors affecting the safety of patients or experimental data collection, as judged by the researchers.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 571, China

Location

MeSH Terms

Interventions

spartalizumab; sintilimab; Capecitabine; Oxaliplatin

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Yuping Zhu, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuping Zhu, MD

CONTACT

86-0571-88128011; drzyp@163.com

Yibo Cai, MD

CONTACT

86-0571-88128011; caiyiyibo@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2020
• First Posted: December 11, 2020
• Study Start: December 1, 2020
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2025
• Last Updated: December 11, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)