Short-Course Radiotherapy Followed by Neoadjuvant Chemotherapy and Camrelizumab in Locally Advanced Rectal Cancer (UNION)

Rectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04928807
• Other study ID #: MA-CRC-?-006
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 20, 2021
• Est. completion date: March 20, 2026

Study information

• Verified date: December 2023
• Source: Wuhan Union Hospital, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 231
• Est. completion date: March 20, 2026
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Combination Product:
• Short course radiotherapy sequential camrelizumab and chemotherapy
Short course radiotherapy, 5 * 5Gy, once a day, 5Gy each time, for 5 days, continuous irradiation, three-dimensional 3D-CRT or IMRT technology is recommended camrelizumab 200 mg , D1, intravenous drip, q3w, 2 cycles before operation, postoperative adjuvant treatment, the longest medication time of camrelizumab was less than 1 year during the whole study period; Capecitabine 1000 mg / m2, twice a day, oral, 1-14 days, then rest for 7 days, q3w, 2 cycles before operation and 6 cycles after operation; Oxaliplatin 130 mg / m2, D1, intravenous infusion 2 hours, q3w, 2 cycles before operation, 6 cycles after operation

Locations

Country	Name	City	State
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (2)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China	Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pathological complete response (pCR) rate	Pathological complete response rate (PCR) assessed by the blind Independent Review Committee, defined as the absence of viable tumour cells in the resected primary tumour specimen and all sampled regional lymph nodes (ypT0N0)	an expected average of 5 months
Secondary	3-year event-free survival rate	The percentage of patients without disease recurrence or progression or death due to any cause after 3-year follow-up	an expected average of 3 years
Secondary	Overall Survival	The time from the date of randomization to the death caused by any cause	an expected average of 5 years
Secondary	R0 resection rate	The rate of negative margin microscopically	an expected average of 2 years
Secondary	3-year disease-Free Survival	The time from the first day of disease free (operation date) to local or distant recurrence, or the death event caused by any reason, whichever occurs first	an expected average of 3 years
Secondary	dverse events (AEs) were graded according to the NCI CTCAE version 5·0	Adverse events and surgical safety	an expected average of 1.5 years