Esophageal Squamous Cell Carcinoma (ESCC)
Conditions
Keywords
Esophageal Squamous Cell Carcinoma, Chemo-Immunotherapy, Induction Therapy, Concurrent Chemoradiotherapy, PD-1 Inhibitor
Brief summary
This is a prospective, randomized, phase II clinical study in patients with unresectable stage III-IVA esophageal squamous cell carcinoma (ESCC). Eligible patients will be randomly assigned in a 1:1 ratio to two treatment groups. The experimental group will receive 3 cycles of induction therapy with PD-1 antibody plus chemotherapy, followed by radiotherapy, and then maintenance therapy with PD-1 antibody monotherapy. The control group will receive concurrent chemoradiotherapy, followed by maintenance therapy with PD-1 antibody monotherapy. The primary endpoints are the complete response (CR) rate at 3 months after radiotherapy (assessed by investigators) and the 1-year progression-free survival (PFS) rate. Secondary endpoints include overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR), local-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), quality of life, and safety profile.
Detailed description
This is a prospective, randomized, two-arm, phase II clinical trial investigating induction chemo-immunotherapy followed by sequential radiotherapy versus concurrent chemo-immunotherapy plus radiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Current standard of care for unresectable locally advanced ESCC is definitive concurrent chemoradiotherapy. However, outcomes remain suboptimal, with high rates of local recurrence and distant metastasis. The addition of PD-1 inhibitors to concurrent chemoradiotherapy has shown promising activity in recent studies, but optimal sequencing and integration of immunotherapy with radiotherapy are still under investigation. This trial is designed to evaluate whether an induction strategy with chemo-immunotherapy followed by radiotherapy can improve response rates and long-term survival compared to the standard concurrent approach. Patients will be randomized to receive either: * Experimental arm: Three cycles of induction chemo-immunotherapy, followed by definitive thoracic radiotherapy, then maintenance immunotherapy for up to one year. * Control arm: Concurrent chemo-immunotherapy plus definitive thoracic radiotherapy, followed by maintenance immunotherapy for up to one year. The primary objective is to compare the efficacy of the two regimens in terms of complete response and progression-free survival. Safety, tolerability, and quality of life will also be assessed to support the risk-benefit profile of each strategy.
Interventions
DRUGPaclitaxel plus Cisplatin or Carboplatin (Induction Chemotherapy)
Paclitaxel 150-175 mg/m² combined with cisplatin 75 mg/m² or carboplatin AUC 5 (maximum 600 mg), administered intravenously every 3 weeks for 3 cycles, concurrent with PD-1 antibody induction therapy for unresectable stage III-IVA esophageal squamous cell carcinoma.
DRUGWeekly Paclitaxel plus Cisplatin or Carboplatin (Concurrent Chemotherapy)
Paclitaxel 50 mg/m² combined with cisplatin 25 mg/m² or carboplatin AUC 5 (maximum 600 mg), administered intravenously once weekly for 5 cycles, concurrent with thoracic radiotherapy (50.4Gy in 28 fractions) for unresectable stage III-IVA esophageal squamous cell carcinoma.
Sponsors
Second Affiliated Hospital of Zunyi Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a randomized, double-blind, parallel-group phase II trial comparing chemo-immunotherapy induction followed by radiotherapy versus concurrent chemoradiotherapy in patients with unresectable stage III-IVA esophageal squamous cell carcinoma.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed unresectable stage III-IVA esophageal squamous cell carcinoma (ESCC) * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Adequate organ function (bone marrow, liver, renal, cardiac) within 2 weeks prior to randomization * Measurable or evaluable disease per RECIST 1.1 * Willing to provide written informed consent
Exclusion criteria
* Previous radiotherapy to the chest or previous systemic chemotherapy for ESCC * History of other malignancies within the last 5 years (except cured basal cell carcinoma or cervical carcinoma in situ) * Severe comorbidities (uncontrolled hypertension, NYHA class III-IV heart failure, active infection, etc.) * Known hypersensitivity to any study drugs (paclitaxel, cisplatin/carboplatin, PD-1 antibody) * Pregnant or lactating women * Participation in another clinical trial within 30 days prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate at 3 Months After Radiotherapy (Investigator-Assessed) | 3 months after completion of radiotherapy | Proportion of patients achieving complete response (CR) per RECIST 1.1, assessed by investigators at 3 months after completion of radiotherapy |
| 1-Year Progression-Free Survival (PFS) Rate | 1 year after randomization | Proportion of patients alive and without disease progression at 1 year after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 3 years after randomization | Time from randomization to death from any cause |
| Progression-Free Survival (PFS) | Up to 3 years after randomization | Time from randomization to first documented disease progression or death from any cause, whichever occurs first |
| Duration of Response (DOR) | Up to 3 years after randomization | Time from first documentation of objective response (CR/PR) to first documented disease progression or death |
| Objective Response Rate (ORR) | Up to 3 years after randomization | Proportion of patients achieving CR or partial response (PR) per RECIST 1.1 |
| Local Regional Failure-Free Survival (LRFS) | Up to 3 years after randomization | Time from randomization to first local or regional recurrence or death |
| Distant Metastasis-Free Survival (DMFS) | Up to 3 years after randomization | Time from randomization to first distant metastasis or death |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | From first study treatment to 30 days after last treatment | Incidence and severity of TEAEs (graded per CTCAE 5.0) during treatment and follow-up |
| EORTC QLQ-OES18 Symptom Score Change | Baseline, 3 months, 6 months, 12 months after radiotherapy | Change in esophageal cancer-specific symptom score as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Oesophageal 18 (EORTC QLQ-OES18) from baseline to post-treatment follow-ups. The scale ranges from 0 to 100, with higher scores indicating more severe symptoms and worse quality of life. |
| EORTC QLQ-C30 Quality of Life Score Change | Baseline, 3 months, 6 months, 12 months after radiotherapy. | Change in quality of life score as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) from baseline to post-treatment follow-ups. The scale ranges from 0 to 100, with higher scores indicating better quality of life. |
Countries
China
Contacts
CONTACTJian-Guo Zhou, PhD
PRINCIPAL_INVESTIGATORLei Zhou, Master
The Second Affiliated Hospital of Zunyi Medical University
Outcome results
None listed