SHR-1701 in Combination With Chemotherapy and Radiotherapy in Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of SHR-1701 combined with radiotherapy and chemotherapy as perioperative treatment for locally advanced rectal cancer. Eligible patients will receive standard chemoradiation with SHR-1701 followed by XELOX combined with SHR-1701. In all subjects, restaging pelvic MRI with chest and abdominal CT will be performed after completion of neoadjuvant treatment to determine resectability and to rule out any evidence of metastases. Subjects who have resectable disease will undergo surgery. Adjuvant XELOX combined with SHR-1701 will be given after surgery.

Official Title
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SHR-1701 in Combination With Radiotherapy and Chemotherapy as Perioperative Treatment for Resectable Locally Advanced Rectal Cancer, an Open Label, Single-arm, Multicenter Phase II Trial

Conditions
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Locally Advanced Rectal Cancer

Intervention / Treatment
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* Drug: SHR-1701；Capecitabine；Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be willing and able to provide written informed consent for the trial. Locally advanced rectal adenocarcinoma and was evaluated as resectable ; The inferior margin of the tumor ≤ 10 cm from the anal verge ; No prior anti-cancer treatment for rectal cancer; Estern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 or 1; Adequate hematologic and end-organ function; Contraception was initiated from the signing of the informed consent until at least 6 months after the last dosing of the study drug Exclusion Criteria: Unresectable disease determined by investigators Recurrent rectal cancer Evidence of metastatic disease or lateral lymph node metastases Presence of synchronous colorectal cancer Presence of obstruction or imminent obstruction Not eligible for long-course radiotherapy Severe cardiovascular and cerebrovascular diseases;Have clinical heart symptoms or diseases that are not well controlled Prior malignancy within the prior 5 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical/breast cancer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A multicenter, open, single-arm, two-stage phase II clinical study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perioperative treatment<br>Eligible subjects will receive standard chemoradiotherapy with SHR-1701 followed by XELOX combined with SHR-1701 and surgery. Adjuvant XELOX combined with SHR-1701 will be given after surgery. | Drug: SHR-1701；Capecitabine；Oxaliplatin<br>* Radiation: Radiation therapy 50.4Gy in 28 fractions to the pelvis on Days 1-5 every week. Drug: Capecitabine Capecitabine 825mg/m^2 orally twice daily (bid) 5 days/week during radiotherapy. Drug:SHR-1701 Drug: Capecitabine (XELOX) Capecitabine 1000mg/m^2 orally twice daily (bid) day1-day14, q3w. Drug: Oxaliplatin Oxaliplatin 130mg/m^2, day1, iv, q3w<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 |  | At week 16, DAY1 | 
| Percentage of participants with Pathological complete response ( pCR ) |  | At week 16, DAY1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor regression grade ( TRG ) |  | At week 16, DAY1 | 
| Percentage of participants with R0 Resection ( R0 ) |  | At week 16, DAY1 | 
| Percentage of participants with Clinical complete response ( cCR ) rate. |  | At week 16, DAY1 | 
| Event-free survival ( EFS ) |  | Year 1, Year 2, Year 3 | 
| Overall survival ( OS ) |  | Year 1, Year 2, Year 3 | 
| Disease-free survival ( DFS ) |  | Year 1, Year 2, Year 3 |