Combining chemoradiotherapy with sintilimab for advanced rectal cancer

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

This study is testing if combining a new immunotherapy drug with standard treatment can help adults with advanced rectal cancer see better results and improve their health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 51 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: sintilimab, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05450029 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the safety and efficacy of sintilimab, an anti-PD-1 immunotherapy, in combination with neoadjuvant chemoradiotherapy for patients with intermediate or high Immunoscore locally advanced rectal cancer. The study aims to determine how well this combination treatment works in facilitating tumor regression and improving patient outcomes. Participants must be treatment-naive adults with specific staging of rectal adenocarcinoma and a defined performance status. The trial is designed to provide insights into the relationship between Immunoscore and response to PD-1 blockade.

Who should consider this trial

Good fit: Ideal candidates are treatment-naive adults aged 18 to 75 with intermediate or high Immunoscore locally advanced rectal cancer.

Not a fit: Patients with complicated primary tumors or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and survival rates for patients with advanced rectal cancer.

How similar studies have performed: Other studies have shown promising results with immunotherapy approaches in similar cancer types, suggesting potential for success in this novel combination.

Eligibility criteria

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.

Where this trial is running

Guangzhou, Guangdong

• Department of colorectal surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Liang Kang, PhD,MD — Sixth Affiliated Hospital, Sun Yat-sen University
• Study coordinator: Xiaobin Zheng, PhD,MD

Conditions Rectal Cancer; Rectal cancer; Immunoscore; MRD