Sequential Tegafur-gimeracil-oteracil Potassium Capsule (s-1) and Serplulimab Following Concurrent Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

NCT06422858 | Recruiting Phase 2 DMC

• 1 other identifier: STARS-CCRT-ESCC
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase II trial evaluates the efficacy and safety of Serplulimab combined with S1 chemotherapy in patients with inoperable, locally advanced esophageal squamous cell carcinoma after concurrent chemoradiation. The primary endpoint is the one-year progression-free survival rate. Secondary measures include clinical response rates, overall survival, duration of response, and safety profiles. Exploratory goals focus on the potential of biomarkers like PD-L1 and ctDNA to predict treatment outcomes. Treatment involves initial chemoradiation followed by consolidation with Serplulimab and S1, continuing for up to 12 months or until disease progression or unacceptable toxicity.

Conditions

Locally Advanced Inoperable Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• One-Year Progression-Free Survival (PFS)

  The primary outcome measure is the proportion of participants who are alive and free from disease progression at one year after initiating treatment. Progression is defined according to RECIST v1.1 criteria as a 20% increase in the sum of diameters of target lesions, the appearance of new lesions, or the worsening of non-target disease

  1 year

Secondary Outcomes (5)

• Incidence of Clinical Complete Response Rate (cCR) at 3 months after treatment initiation

  Assessed at 3 months after treatment initiation

• Overall Survival (OS)

  From the start of treatment up to 3 years

• Duration of Response (DoR)

  From the first documented response up to 2 years

• Incidence of Treatment-Emergent Adverse Events

  Throughout the study, estimated at 12 months

• EORTC-QoL-C30 Score(Quality of Life)

  At baseline, 6 months, and 12 months

Other Outcomes (1)

• Grade 3 Pneumonia Incidence [Safety and Tolerability]

  through study completion, an average of 1 year

Study Arms (1)

Serplulimab and S1 Chemotherapy Post-Concurrent Chemoradiation

EXPERIMENTAL

Drug: Serplulimab; Drug: Tegafur-gimeracil-oteracil potassium capsule(S1); Radiation: Radiotherapy; Drug: Cisplatin

Interventions

Serplulimab DRUG

Serplulimab will be administered as a fixed dose of 300 mg via intravenous infusion every three weeks, continuing for up to 12 months or until disease progression, unacceptable toxicity, or withdrawal of consent

Serplulimab and S1 Chemotherapy Post-Concurrent Chemoradiation

Tegafur-gimeracil-oteracil potassium capsule(S1) DRUG

S1 will be administered at a dose of 60 mg/m2 per day, taken orally in two divided doses on day 1 concurrent with radiotherapy, repeated every 28 days; and from day 1 to day 14 of each 21-day cycle, for up to 12 months or until disease progression, unacceptable toxicity, or withdrawal of consent

Serplulimab and S1 Chemotherapy Post-Concurrent Chemoradiation

Radiotherapy RADIATION

Radiotherapy will be delivered as a total dose of 50.4 Gy in 28 fractions over six weeks using techniques such as IGRT, IMRT, VMAT, or TOMO, targeting the primary tumor and associated lymph nodes

Serplulimab and S1 Chemotherapy Post-Concurrent Chemoradiation

Cisplatin DRUG

Cisplatin will be administered at a dose of 75 mg/m\^2 on day 1 concurrent with radiotherapy, repeated every 28 days

Serplulimab and S1 Chemotherapy Post-Concurrent Chemoradiation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and voluntarily sign a written informed consent form, which must be signed before initiating any study-specific procedures.
• Male or female participants aged between 18 and 70 years at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Histologically or cytologically confirmed diagnosis of locally advanced esophageal squamous cell carcinoma (ESCC); or patients who refuse surgery; staged as T1-4bN1-3M0 (according to AJCC 8th edition).
• Medically inoperable or refusal of surgery.
• No prior anti-tumor treatment.
• Expected survival of at least 6 months.
• At least one measurable lesion as defined by RECIST v1.1.
• Participants must provide either archived (within the last 2 years) or freshly obtained tumor tissue samples, with at least three unstained FFPE pathology slides.
• Adequate organ function defined as follows:
• a. Hematology (no blood transfusions or growth factor support within 7 days before starting study treatment): i. Absolute Neutrophil Count (ANC) ≥1.5×10\^9/L (1500/mm³); ii. Platelet count ≥100×10\^9/L (100000/mm³); iii. Hemoglobin ≥90 g/L. b. Renal: i. Calculated creatinine clearance (CrCl) ≥50 mL/min using the Cockcroft-Gault formula: CrCl (mL/min) = {(140-age) × weight (kg) × F} / (SCr (mg/dL) × 72), where F=1 for males and 0.85 for females; SCr=serum creatinine.
• ii. Urinary protein \<2+ or 24-hour urinary protein quantification \<1.0 g. c. Liver: i. Total bilirubin (TBiL) ≤1.5×ULN; ii. AST and ALT ≤2.5×ULN (≤5×ULN for participants with liver metastases); iii. Serum albumin (ALB) ≥28 g/L. d. Coagulation: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN, unless the participant is receiving anticoagulant therapy and INR and APTT are within the expected range of their therapeutic use.
• e. Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥50%.
• Female participants of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to the first dose of study medication. If urine test is not conclusive, a serum test will be administered. If sexually active with a non-sterilized male partner, the participant must agree to use effective contraception during the study and for 120 days after the last dose of study medication. Discussion with the researcher is required regarding cessation of contraception after this point.
• Male participants with female partners of childbearing potential must agree to use effective contraception from screening to 120 days after the last dose of study medication. Discussion with the researcher is required regarding cessation of contraception after this point.
• Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Previous anti-tumor treatment (including chemotherapy, radiation therapy, surgery, or immunotherapy).
• Initial diagnosis with metastases to vital organs such as the liver, bones, lungs, brain, adrenal glands, etc. (stage IVb esophageal cancer).
• History of thoracic radiotherapy.
• Presence of an esophageal mediastinal fistula and/or esophageal tracheal fistula before treatment.
• Known or suspected allergy to any component of S1, serplulimab, or cisplatin.
• Pregnant or breastfeeding women.
• Inability to provide informed consent due to psychological, familial, or social reasons.
• History of any malignancy other than esophageal cancer within the past 5 years, except for adequately treated non-melanoma skin cancer, in-situ cervical cancer, or cured early-stage prostate cancer.
• Unable to tolerate chemoradiation due to severe cardiac, pulmonary, hepatic, renal dysfunctions, hematological diseases, or cachexia.
• Active autoimmune diseases, history of autoimmune diseases (including but not limited to colitis, hepatitis, hyperthyroidism, or syndromes), history of immunodeficiency (including positive HIV test), or other acquired or congenital immunodeficiency diseases, history of organ transplant or allogeneic bone marrow transplant.
• Active hepatitis B (HBV DNA ≥ 2000IU/mL or 10×10\^4 copies/mL), positive hepatitis C antibody with elevated HCV RNA levels above the lower limit of detection.
• History of immunodeficiency; positive HIV antibody; current long-term use of systemic corticosteroids or other immunosuppressants.
• Serious infection within 4 weeks before the first administration of study medication, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective treatment within 2 weeks before the first dose (excluding antiviral treatment for hepatitis B or C).
• Vaccination with live or attenuated live vaccines within 30 days before the first dose of study medication or planning to receive such vaccines during the study period; inactivated vaccines are permitted.
• History of interstitial lung disease or non-infectious pneumonia.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

MeSH Terms

Interventions

Radiotherapy; Cisplatin

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yongling Ji

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Wang, Dr

CONTACT

86-571-88122564; wangjin@zjcc.org.cn

Study Design

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

Study Record Dates

• First Submitted: May 9, 2024
• First Posted: May 21, 2024
• Study Start: May 20, 2024
• Primary Completion: December 31, 2025
• Study Completion: April 1, 2026
• Last Updated: May 9, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)