Short-course Radiotherapy Followed by Tislelizumab + CapeOX in the Treatment for Locally Advanced Rectal Cancer

Sponsor

Hebei Medical University Fourth Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05086627

Collaborator

(none)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a single-center, prospective, open-label, randomized controlled clinical study, and the purpose of this study was to compare the pathological complete response rate (PCR) of patients with locally advanced rectal cancer treated with short-course radiotherapy sequential Tislelizumab combined with CapeOX (group A) versus short-course radiotherapy sequential CapeOX (group B). A total of 100 patients with locally advanced rectal cancer will be enrolled in the study. These patients were randomly assigned to the experimental group (group A) and the control group (group B) in a ratio of 1:1.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Rectal Cancer	Drug: Tislelizumab Radiation: Short-course radiotherapy Drug: Capecitabine+Oxaliplatin	Phase 2

Detailed Description

Subjects in group A will be treated according to the following treatment plan:

Surgery: Total mesorectal excision will be performed between day 98 and 105, i.e., between 1 to 2 weeks after completion of Sequential treatment) Postoperative adjuvant chemotherapy: Chemotherapy will be started 4-6 weeks after surgery, and the adjuvant regimen was CapeOX for 2 cycles.

Subjects in group B will be treated according to the following treatment plan:

Surgery: Total mesorectal excision will be performed between day 98 and 105, i.e., between 1 to 2 weeks after completion of Sequential treatment.

Postoperative adjuvant chemotherapy: Chemotherapy will be started 4-6 weeks after surgery, and the adjuvant regimen was CapeOX for 2 cycles.

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)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Single -Centers, Randomized, Open-label, Controlled Phase Ⅱ Clinical Trial of Short-course Radiotherapy Followed by Tislelizumab + CapeOX in the Treatment for Locally Advanced Rectal Cancer

Anticipated Study Start Date :

Oct 15, 2022

Anticipated Primary Completion Date :

May 15, 2024

Anticipated Study Completion Date :

May 15, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Short-course radiotherapy sequential Tislelizumab combined with CapeOX (group A) Standard SCRT: A total radiation dose of 25 Gy was delivered in 5 fractions (from day 1 to 5) Sequential treatment period: After resting for 5 days following completion of SCRT, patients were treated with Tislelizumab (days 11, 33, 55, 77) and neoadjuvant chemotherapy with CapeOX (days 11 to 25, 33 to 47, 55 to 69, and 77 to 91). Surgery: Total mesorectal excision will be performed between day 98 and 105, i.e., between 1 to 2 weeks after completion of Sequential treatment) Postoperative adjuvant chemotherapy: Chemotherapy will be started 4-6 weeks after surgery, and the adjuvant regimen was CapeOX for 2 cycles.	Drug: Tislelizumab Patients were treated with Tislelizumab (days 11, 33, 55, 77) Radiation: Short-course radiotherapy Patients were treated with short-course neoadjuvant radiotherapy Drug: Capecitabine+Oxaliplatin Patients were treated with neoadjuvant chemoherapy with CapeOX
Active Comparator: Short-course radiotherapy sequential CapeOX (group B) Standard SCRT: A total radiation dose of 25 Gy was delivered in 5 fractions (from day 1 to 5) Sequential treatment period: After resting for 5 days following completion of SCRT, patients were treated with neoadjuvant chemotherapy with CapeOX (days 11 to 25, 33 to 47, 55 to 69, and 77 to 91). Surgery: Total mesorectal excision will be performed between day 98 and 105, i.e., between 1 to 2 weeks after completion of Sequential treatment. Postoperative adjuvant chemotherapy: Chemotherapy will be started 4-6 weeks after surgery, and the adjuvant regimen was CapeOX for 2 cycles.	Radiation: Short-course radiotherapy Patients were treated with short-course neoadjuvant radiotherapy Drug: Capecitabine+Oxaliplatin Patients were treated with neoadjuvant chemoherapy with CapeOX

Arm

Intervention/Treatment

Experimental: Short-course radiotherapy sequential Tislelizumab combined with CapeOX (group A)

Standard SCRT: A total radiation dose of 25 Gy was delivered in 5 fractions (from day 1 to 5) Sequential treatment period: After resting for 5 days following completion of SCRT, patients were treated with Tislelizumab (days 11, 33, 55, 77) and neoadjuvant chemotherapy with CapeOX (days 11 to 25, 33 to 47, 55 to 69, and 77 to 91). Surgery: Total mesorectal excision will be performed between day 98 and 105, i.e., between 1 to 2 weeks after completion of Sequential treatment) Postoperative adjuvant chemotherapy: Chemotherapy will be started 4-6 weeks after surgery, and the adjuvant regimen was CapeOX for 2 cycles.

Drug: Tislelizumab

Patients were treated with Tislelizumab (days 11, 33, 55, 77)

Radiation: Short-course radiotherapy

Patients were treated with short-course neoadjuvant radiotherapy

Drug: Capecitabine+Oxaliplatin

Patients were treated with neoadjuvant chemoherapy with CapeOX

Active Comparator: Short-course radiotherapy sequential CapeOX (group B)

Standard SCRT: A total radiation dose of 25 Gy was delivered in 5 fractions (from day 1 to 5) Sequential treatment period: After resting for 5 days following completion of SCRT, patients were treated with neoadjuvant chemotherapy with CapeOX (days 11 to 25, 33 to 47, 55 to 69, and 77 to 91). Surgery: Total mesorectal excision will be performed between day 98 and 105, i.e., between 1 to 2 weeks after completion of Sequential treatment. Postoperative adjuvant chemotherapy: Chemotherapy will be started 4-6 weeks after surgery, and the adjuvant regimen was CapeOX for 2 cycles.

Radiation: Short-course radiotherapy

Patients were treated with short-course neoadjuvant radiotherapy

Drug: Capecitabine+Oxaliplatin

Patients were treated with neoadjuvant chemoherapy with CapeOX

Outcome Measures

Primary Outcome Measures

Pathological complete response rate [1 week after surgery]
Pathological complete response rate was defined as the absence of viable tumour cells in the resected primary tumour specimen and all sampled regional lymph nodes (ypT0N0)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients or their family members agree to participate in the study and sign the informed consent form;

Patients ≥ 18 and ≤75 years old, male or female;

ECOG performance status of 0 or 1;

Patients with histologically confirmed rectal adenocarcinoma;

The clinical diagnosis of chest CT, abdomen and enhanced MRI was cT3/T4a, Nany, M0;

The distance between the lower edge of the tumor and the anal edge is less than or equal to 10 cm;

No history of immune system diseases;

No history of immunodeficiency, including HIV positive;

No history of other malignancies;

No history of myocarditis;

No history of cardiovascular and cerebrovascular diseases;

No history of thyroid dysfunction;

No history of liver and kidney diseases;

No history of mental illness, no history of Infectious diseases;

No history of organ transplantation or allogeneic bone marrow transplantation;

There is no history of other systemic diseases other than the above diseases;

Voluntarily accept the neoadjuvant treatment scheme of radiotherapy, sequential chemotherapy / chemotherapy combined with immunotherapy;

Swallowing pills normally;

Rectal cancer without radiotherapy, chemotherapy, surgery, Chinese medicine anti-tumor treatment, etc.;

Surgical treatment is planned after neoadjuvant treatment.

Exclusion Criteria:

Patients who do not meet the above inclusion criteria;

Documented history of allergy to study drugs, including any component of Tislelizumab, capecitabine, oxaliplatin and other platinum drugs;

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; Major surgery or severe trauma within 4 weeks before the first use of the study drug;

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;

Female patients who is pregnant or breastfeeding;

Patients who refuse to sign informed consent by themselves or their authorized persons;

Patients with poor cognitive ability, unable to answer questions, unable to fill in questionnaires or mental disorders;

Patients considered unsuitable for the study by the investigator.