Clinical trial NCT04928807: Short-Course Radiotherapy Followed by Neoadjuvant Chemotherapy and Camrelizumab in Locally Advanced Rectal Cancer (UNION)
Official title: A Multicenter, Randomized, Open-label, Controlled Phase III Clinical Trial of Short-Course Radiotherapy Followed by Neoadjuvant Chemotherapy and Camrelizumab in the Treatment for Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Rectal Cancer
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2021-06-16
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a multicenter, open-label, randomized controlled clinical study, and the purpose of the study is to compare the pathological complete response rate (PCR) of patients with locally advanced rectal cancer treated with short-term radiotherapy, sequential Camrelizumab and CAPOX (group A) to long-term concurrent chemoradiotherapy, sequential CAPOX (group B) in patients with LARC. A total of 230 patients were included in this study.

Detailed description: Patients with locally advanced rectal cancer (T3-4/N+) were randomly assigned to experimental group A or control group B according to the ratio of 1:1,who will receive preoperative neoadjuvant therapy, and the Primary endpoint of the study is Pathological complete response rate(PCR ) assessed by the blind independent review committee (BIRC), defined as the absence of viable tumour cells in the resected primary tumour specimen and all sampled regional lymph nodes (ypT0N0)

Eligibility criteria: Inclusion Criteria:

1. Patients or their family members agree to participate in the study and sign the informed consent form;
2. Age 18-75 years, male or female;
3. Histologically confirmed T3-44 and/or N+ rectal adenocarcinoma (AJCC/UICC TNM staging (8th Edition, 2017);
4. inferior margin ≤ 10 cm from the anal verge;
5. It is expected to reach R0;
6. ECOG performance status score is 0-1;
7. Swallowing pills normally;
8. Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc;
9. Surgical treatment is planned after neoadjuvant treatment;
10. There was no operative contraindication;
11. Laboratory tests were required to meet the following requirements:

    white blood cell (WBC) ≥ 4×109/L; Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥90 g/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance rate ≥50 mL/min; International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN
12. Males or females with reproductive ability who are willing to use contraception in the trial;

Exclusion Criteria:

1. Documented history of allergy to study drugs, including any component of Camrelizumab, capecitabine, irinotecan, oxaliplatin and other platinum drugs;
2. Have received or are receiving any of the following treatments:

   Any radiotherapy, chemotherapy or other anti-tumor drugs for tumor; Patients who need to be treated with corticosteroid (dose equivalent to prednisone of \>10 mg/day) or other immunosuppressive agents within 2 weeks prior to study drug administration; Received live attenuated vaccine within 4 weeks before the first use of the study drug; Major surgery or severe trauma within 4 weeks before the first use of the study drug;
3. Any active autoimmune disease or history of autoimmune disease;
4. Have a history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation or allogeneic bone marrow transplantation;
5. There are clinical symptoms or diseases of heart that are not well controlled;
6. Severe infection (CTCAE \> 2) occurred within 4 weeks before the first use of the study drug; Baseline chest imaging revealed active pulmonary inflammation, signs and symptoms of infection within 14 days prior to the first use of the study drug, or oral or intravenous antibiotic therapy, except for prophylactic use of antibiotics;
7. Patients with active pulmonary tuberculosis infection found by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within one year before enrollment, or with a history of active pulmonary tuberculosis infection more than one year ago but without regular treatment;
8. The presence of active hepatitis B (HBV DNA \> 2000 IU/mL or 104 copies/mL) was positive for hepatitis C (hepatitis C antibody) and HCV RNA was higher than the lower limit of analytical method;
9. Female subject who is pregnant or breastfeeding;
10. Patients who are not suitable for participation in clinical trials in the opinion of the investigator

Primary outcomes:
measure: pathological complete response (pCR) rate
timeFrame: an expected average of 5 months
Secondary outcomes:
measure: 3-year event-free survival rate
timeFrame: an expected average of 3 years
measure: Overall Survival
timeFrame: an expected average of 5 years
measure: R0 resection rate
timeFrame: an expected average of 2 years
measure: 3-year disease-Free Survival
timeFrame: an expected average of 3 years
measure: dverse events (AEs) were graded according to the NCI CTCAE version 5·0
timeFrame: an expected average of 1.5 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Tao Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: