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

NCT05450029 | Recruiting Phase 2 DMC

• 1 other identifier: GIHSYSU-25
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rectal Cancer

Keywords

Rectal cancer; Immunoscore; MRD

Outcome Measures

Primary Outcomes (1)

• Pathological complete response

  Pathological complete response will be evaluated with American Joint Committee on Cancer (AJCC) Cancer Staging

  1 month after surgery

Secondary Outcomes (8)

• Margin-free (R0) resection rate

  Immediately after the surgery

• 3-year event-free survival rate

  3 years after the surgery

• 3-year overall survival rate

  3 years after the surgery

• Local recurrence

  3 years after the surgery

• Tumor downstaging

  during the 3-year period of follow-up

Study Arms (1)

Chemoradiotherapy and PD1 inhibitor

EXPERIMENTAL

Chemoradiotherapy and PD1 inhibitor

Drug: Sintilimab

Interventions

Sintilimab DRUG

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).

Also known as: Chemoradiotherapy and PD1 inhibitor

Chemoradiotherapy and PD1 inhibitor

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and ≤75 years.
• Willing and able to provide written informed consent for participation in this study.
• Treatment-naive patients with histological or cytological documentation of rectal adenocarcinoma (\<12 cm from the anal verge).
• Clinical stage of T3/T4 or N positive and M0, before nCRT.
• Non complicated primary tumor (complete obstruction, perforation, bleeding).
• Subjects with an intermediate or high immunoscore (according to Immunoscore®).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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.
• Women of childbearing potential with a negative serum or urine pregnancy test within 24 hours prior to the start of study drug.
• 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).

You may not qualify if:

• Subjects with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer.
• 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).
• Subjects with active lung disease (such as interstitial pneumonia, pneumonia, obstructive pulmonary disease, asthma) or active tuberculosis.
• 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.
• Subjects with a history of anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy.
• Subjects with known allergy to the study drugs or to any of its excipients.
• Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
• Breast- feeding or pregnant women.
• 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.

Sponsors & Collaborators

• Yanhong Deng: lead
• GeneCast Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Department of colorectal surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510000, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

sintilimab; Chemoradiotherapy; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Liang Kang, PhD,MD

  Sixth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaobin Zheng, PhD,MD

CONTACT

02038455369; zhengxbn@mail3.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 20, 2022
• First Posted: July 8, 2022
• Study Start: January 1, 2022
• Primary Completion: January 1, 2024
• Study Completion (Estimated): January 1, 2027
• Last Updated: September 26, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)