Sintilimab After Concurrent Chemoradiotherapy in Elderly Patients With Unresectable Esophageal Squamous Cell Carcinoma: A Randomized, Multi-center Phase II Clinical Trial
Overview
- Phase
- Phase 2
- Intervention
- Sintilimab
- Conditions
- Esophageal Cancer
- Sponsor
- Zhejiang Cancer Hospital
- Enrollment
- 191
- Locations
- 1
- Primary Endpoint
- mPFS
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This trial is a prospective, randomized, controlled, multicenter, phase II clinical study to evaluate the efficacy and safety of sintilimab as consolidation therapy in elderly patients with esophageal cancer who did not progress after concurrent chemoradiotherapy.
Patients aged 70-85 years with esophageal squamous cell carcinoma who did not progress after concurrent chemoradiotherapy and meet the inclusion criteria will be stratified according to MRD status (positive vs negative) and randomized in a 1:1 ratio into two groups: the treatment group receiving sintilimab (for patients with a weight <60 kg: 3 mg/kg IV on Day 1 every 3 weeks; for patients with a weight ≥60 kg: 200 mg IV on Day 1 every 3 weeks) and the observation group receiving regular follow-up. Patients should receive the first dose within 42 days after completing the last radiotherapy session and continue treatment until disease progression, intolerable toxicity, loss to follow-up, death, or other circumstances where the investigator determines treatment should be discontinued, whichever occurs first. The maximum duration of sintilimab treatment is 12 months (from the start of treatment), while the observation group will be followed up every 3 months for at least one year. No other anti-tumor treatments are allowed during the study period. The study aims to compare the effects of the two treatment modalities on progression-free survival, overall survival, tumor response, toxicity reactions, and quality of life in elderly patients with esophageal cancer.
Investigators
Yang Yang
Clinical Professor
Zhejiang Cancer Hospital
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed squamous cell carcinoma of the esophagus, clinically staged before treatment (8th edition of the UICC/AJCC TNM staging system for esophageal squamous cell carcinoma) as stage II-IVb (cT1N2-3M0-1, cT2-4bN0-3M0-1, M1 limited to supraclavicular lymph node metastasis).
- •Candidates for curative esophageal cancer surgery who are unable to tolerate surgery or refuse surgery.
- •Age 70 to 85 years.
- •ECOG performance status of 0-
- •The minimum technical standard for radiotherapy is intensity-modulated radiotherapy (IMRT). The total dose of radiotherapy is 54Gy ± 10%.
- •Note: It is recommended that study centers conduct screening within 14 days after subjects complete synchronous chemoradiotherapy.
- •Concurrent chemotherapy regimen: Single-agent S-1 70mg/m2, days 1-14 and 29-42, synchronized with radiotherapy for 14 days or longer.
- •The last cycle of chemotherapy must end before or concurrently with the last session of radiotherapy. Consolidation chemotherapy after radiotherapy is not allowed, and chemotherapy before chemoradiotherapy is not accepted. Patients who have not progressed after chemoradiotherapy, including complete response (CR), partial response (PR), and stable disease (SD), can be enrolled in this study.
- •Except for hearing loss, hair loss, and fatigue, all toxicities from previous anti-tumor treatments must have recovered to grade ≤1 (according to the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) or baseline level before enrollment.
- •The first dose of study medication must be administered within 42 days after completion of chemoradiotherapy.
Exclusion Criteria
- •Patients who underwent surgical resection for esophageal cancer prior to the start of this trial or have previously received treatment with immune checkpoint inhibitors such as anti-PD-1/PD-L1 or CTLA-4 inhibitors.
- •Patients staged as cT1-3N1-2M0, deemed suitable for surgical resection, and requiring surgery.
- •Experience disease progression after chemoradiotherapy.
- •High risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation.
- •History of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, or other uncontrolled acute pulmonary conditions.
- •Poor nutritional status, with a BMI less than 18.5kg/m2, or PG-SGA score ≥
- •Inability to comprehend trial requirements or likelihood of non-compliance with trial requirements.
- •Presence of hematogenous metastases.
- •Presence of other malignant lesions, excluding curable non-melanoma skin cancer, cervical carcinoma in situ, or malignancies with a cure ≥5 years.
- •Known grade 3 to 4 allergic reactions to any treatment component.
Arms & Interventions
Sintilimab group
Patients in treatment group receive sintilimab (for patients with a weight \<60 kg: 3 mg/kg IV on Day 1 every 3 weeks; for patients with a weight ≥60 kg: 200 mg IV on Day 1 every 3 weeks) .
Intervention: Sintilimab
Outcomes
Primary Outcomes
mPFS
Time Frame: The time from the start of treatment, for half of the participants in a study to experience disease progression or death from any cause
Median Progression-free survival (PFS) assessed in the intention-to-treat (ITT) population according to RECIST 1.1 criteria.
Secondary Outcomes
- ORR(2 months after enrollment)
- OS(occurence or end of follow-up（2 years after enrollment）, which comes first)
- DoR(occurence or end of follow-up（2 years after enrollment）, which comes first)