Neoadjuvant Chemoradiotherapy Plus Sintilimab for Intermediate/High Immunoscore Locally Advanced Rectal Cancer (SILAR)

Neoadjuvant Chemoradiotherapy Plus Sintilimab for Intermediate/High Immunoscore Locally Advanced Rectal Cancer: A Single-Center, Open-Label, Single-Arm, Phase 2 Trial

Immunoscore has been reported to be superior to microsatellite instability staging in predicting the disease-specific recurrence and survival for patients with colorectal cancer. However, the relationship between Immunoscore and its impact on patient's response to PD-1 blockade remains to be elucidated. This phase II, prospective, open label study is designed to evaluate the efficacy and safety of combination neoadjuvant chemoradiotherapy (nCRT) with the anti-PD-1 antibody sintilimab for intermediate/high Immunoscore locally advanced rectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Sintilimab

Detailed Description

This study investigates the safety, tolerability, and feasibility of sintilimab, an immunotherapy agent, in combination with nCRT for treatment of patients with intermediate/high Immunoscore locally advanced rectal cancer. Sintilimab is an anti-PD-1 inhibitor that works by enhancing the functional activity of the target immune cells to facilitate tumor regression and ultimately immune rejection.

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaobin Zheng, PhD,MD; Phone Number: 02038455369; Email: zhengxbn@mail3.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University
      • Contact: Liang Kang, MD, PhD; Phone Number: 008613602886833; Email: eonkang@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years and ≤75 years.
2. Willing and able to provide written informed consent for participation in this study.
3. Treatment-naive patients with histological or cytological documentation of rectal adenocarcinoma (<12 cm from the anal verge).
4. Clinical stage of T3/T4 or N positive and M0, before nCRT.
5. Non complicated primary tumor (complete obstruction, perforation, bleeding).
6. Subjects with an intermediate or high immunoscore (according to Immunoscore®).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Women of childbearing potential who consent to practicing contraception during the period from giving informed consent to at least 23 weeks after the last dose of therapy.
9. Women of childbearing potential with a negative serum or urine pregnancy test within 24 hours prior to the start of study drug.
10. Subjects with normal organ and marrow function as defined below:

Leukocytes ≥ 3,000/k/uL; Absolute neutrophil count ≥ 1,500/k/uL; Platelet count ≥ 100,000/k/uL; Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); AST (SGOT) ≤ 2.5 x institutional upper limit of normal (ULN); ALT (SGPT) ≤ 2.5 x institutional upper limit of normal (ULN); Serum creatinine ≤ 1.5 x institute upper limit of normal (ULN).

Exclusion Criteria:

1. Subjects with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer.
2. Subjects with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), myocardial infarction (MI), Transient Ischemic Attacks (TIA), or cerebralvascular accident (CVA).
3. Subjects with active lung disease (such as interstitial pneumonia, pneumonia, obstructive pulmonary disease, asthma) or active tuberculosis.
4. Subjects with any uncontrollable clinical problems, including but not limited to: active autoimmune disease, uncontrolled diabetes, uncontrolled hypertension, heart failure grade III/IV (NYHA-classification), or persistent or severe infection.
5. Subjects with a history of anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy.
6. Subjects with known allergy to the study drugs or to any of its excipients.
7. Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
8. Breast- feeding or pregnant women.
9. Subjects with significant unstable mental diseases or other medical diseases that may interfere with the safety of the subjects, obtaining informed consent, or compliance with the procedures for the clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Chemoradiotherapy and PD1 inhibitor

Drug: Sintilimab; 6 cycles of mFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) followed by long course chemoradiotherapy (50 Gy in 25 fractions) followed by surgery. Patients will receive sintilimab 3mg/kg every 2 weeks during chemoradiotherapy (2nd-6th cycle).; Other Names: Chemoradiotherapy and PD1 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response	Pathological complete response will be evaluated with American Joint Committee on Cancer (AJCC) Cancer Staging	1 month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year event-free survival rate		3 years after the surgery
3-year overall survival rate		3 years after the surgery
Local recurrence	Defined as an intrapelvic recurrence following a primary rectal cancer resection, with or without distal metastasis.	3 years after the surgery
Margin-free (R0) resection rate		Immediately after the surgery
Tumor downstaging		during the 3-year period of follow-up
Tumor regression grade		during the 3-year period of follow-up
Number of participants with surgical complications		30 days after surgery
Correlation between minimal residual disease (MRD) and survival	The correlation between the status of MRD and the tumor local recurrence and metastasis.	3 years after the surgery

Collaborators and Investigators

• Sponsor: Yanhong Deng
• Collaborators: GeneCast Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Liang Kang, PhD,MD, Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: June 20, 2022
• First Submitted That Met QC Criteria: July 4, 2022
• First Posted (Actual): July 8, 2022

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 24, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Rectal cancer; MRD; Immunoscore
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors
• Other Study ID Numbers: GIHSYSU-25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No