Trial Title:
Sequential Tegafur-gimeracil-oteracil Potassium Capsule (s-1) and Serplulimab Following Concurrent Chemoradiotherapy for Esophageal Squamous Cell Carcinoma
NCT ID:
NCT06422858
Condition:
Locally Advanced Inoperable Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Tegafur
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Serplulimab
Description:
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
Arm group label:
Serplulimab and S1 Chemotherapy Post-Concurrent Chemoradiation
Intervention type:
Drug
Intervention name:
Tegafur-gimeracil-oteracil potassium capsule(S1)
Description:
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
Arm group label:
Serplulimab and S1 Chemotherapy Post-Concurrent Chemoradiation
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
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
Arm group label:
Serplulimab and S1 Chemotherapy Post-Concurrent Chemoradiation
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin will be administered at a dose of 75 mg/m^2 on day 1 concurrent with
radiotherapy, repeated every 28 days
Arm group label:
Serplulimab and S1 Chemotherapy Post-Concurrent Chemoradiation
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.
Detailed description:
Detailed Description:
This single-arm, Phase II study is designed to assess the efficacy and safety of the
combination of Serplulimab (an anti-PD-1 antibody) and S1 (an oral fluoropyrimidine
derivative) in patients with locally advanced, inoperable esophageal squamous cell
carcinoma (ESCC), following concurrent chemoradiation therapy.
Study Treatment Regimen:
Patients enrolled in the study will first undergo concurrent chemoradiation, which
includes a total radiation dose of 50.4 Gy delivered in 28 fractions over six weeks.
Radiation will be administered using modern techniques such as image-guided radiation
therapy (IGRT), intensity-modulated radiation therapy (IMRT), volumetric modulated arc
therapy (VMAT), or helical tomotherapy (TOMO), ensuring precise targeting of the tumor
and surrounding lymph nodes. Concurrent chemotherapy consists of cisplatin (75 mg/m2 on
day 1) and S1 (60 mg/m2 per day, given in two divided doses from day 1 to day 14,
repeated every 28 days).
Following chemoradiation, patients will receive consolidation therapy with Serplulimab
administered at a fixed dose of 300 mg every three weeks via intravenous infusion,
alongside S1 (60 mg/m2 per day, on days 1-14 of a 21-day cycle). This consolidation phase
will continue for up to 12 months or 17 cycles, unless there is disease progression,
patient withdrawal, onset of unacceptable toxicity, or initiation of new anti-cancer
treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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).
Known active tuberculosis (TB), suspected active TB requiring clinical exclusion; known
active syphilis infection.
- 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.
- History of myocarditis, cardiomyopathy, malignant arrhythmias, unstable angina,
myocardial infarction within the past 12 months, congestive heart failure as
determined by NYHA Class II or higher, or vascular diseases such as aortic aneurysm
at risk of rupture, or other cardiac damage that could compromise the safety
evaluation of the study medication (such as poorly controlled arrhythmia or
myocardial ischemia).
- Known history of mental illness, drug abuse, alcoholism, or drug addiction.
- Non-malignant systemic diseases or symptoms secondary to tumors that could pose a
higher medical risk or confound the assessment of survival, such as leukemic
reaction (white cell count >20×10^9/L) or cachexia manifestations (known weight loss
exceeding 10% in the 3 months prior to screening).
- Any condition that, in the opinion of the investigator, might pose a risk to the
participant, interfere with the evaluation of the study medication, or confound the
interpretation of study results.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hangzhou
Zip:
310022
Country:
China
Status:
Recruiting
Contact:
Last name:
Jin Wang, MD
Phone:
0086-571-88122088
Email:
duxianghui88@yahoo.com.cn
Contact backup:
Last name:
Yongling JI, MD
Phone:
0086-571-88122088
Email:
drjyl@msn.com
Investigator:
Last name:
Yongling JI, MD
Email:
Principal Investigator
Start date:
May 2024
Completion date:
April 2026
Lead sponsor:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Source:
Zhejiang Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06422858
