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

Sponsor

Zhejiang Cancer Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04663763

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Rectal Cancer	Drug: PD-1 antibody Drug: Capecitabine Drug: Oxaliplatin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Combination of Neoadjuvant Short-course Radiotherapy and Immunotherapy in Locally Advanced Rectal Cancer：A Open-label Single-arm Phase II Trial.

Anticipated Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neoadjuvant short-course radiotherapy+immunotherapy+chemotherapy 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 Sintilimab is a humanized IgG4 monoclonal antibody against the programmed death-1 (PD-1) receptor. Usage: 200mg ivgtt d1 q3w. Other Names: Sintilimab Drug: Capecitabine Usage: 1000mg/m2 d1-14 q3w Drug: Oxaliplatin Usage: 130mg/m2 d1 q3w

Arm

Intervention/Treatment

Experimental: Neoadjuvant short-course radiotherapy+immunotherapy+chemotherapy

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

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

Other Names:

Sintilimab

Drug: Capecitabine

Usage: 1000mg/m2 d1-14 q3w

Drug: Oxaliplatin

Usage: 130mg/m2 d1 q3w

Outcome Measures

Primary Outcome Measures

pCR 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]
Pathologic complete response rate

Secondary Outcome Measures

3-year DFS [Assessed up to 3 years]
3-year disease free survival rate
3-year local recurrence rate [Assessed up to 3 years]
3-year local recurrence rate
3-year OS [Assessed up to 3 years]
3-year overall survival rate
Grade 3-4 adverse effects rate [Assessed up to 3 years]
Radiotherapy, immunotherapy and chemotherapy related grade 3-4 adverse events rate
Surgical complications [Assessed up to 3 years from the TME surgery]
Type and Rate of surgical complications
Quality of Life Scale [Assessed up to 5 years]
The Quality of Life Scale (QoLS, range 0-60) will be used to evaluate the quality of life. Higher scores mean the better quality of life

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. 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.

Exclusion Criteria:

1. 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.