Radiotherapy Combined With Immunochemotherapy in Metastatic Esophageal Squamous Cell Carcinoma

Sponsor

Shanghai Chest Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05978193

Collaborator

(none)

160

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

SCR-ESCC-01 is a multicenter, randomized, phase II study aiming to investigate the benefit of early involvement of low-dose radiotherapy(LDRT) and conventionally fractionated radiotherapy(CFRT) in the first-line anti-PD-1 based treatment of metastatic ESCC.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Squamous Cell Carcinoma Esophageal Cancer Metastatic Esophageal Squamous Cell Carcinoma	Radiation: LDRT+CFRT Drug: Immunotherapy Drug: Chemotherapy	Phase 2

Detailed Description

In metastatic esophageal cancer, radiotherapy is often administered for palliative purposes to alleviate the symptom of dysphagia. Recent studies have shown that the combination of radiotherapy and immunotherapy may have a synergistic effect on treatment outcomes. The study aims to investigate the benefit of LDRT in combination with conventionally fractionated radiotherapy (CFRT) in improving the outcome of metastatic ESCC concurrently treated with first-line immunochemotherapy. The recruited patients will be randomly (1:1) assigned to receive either PD-1 inhibitor plus chemotherapy (paclitaxel and platinum regimen) (arm B) or in combination with LDRT and CFRT (arm A). The primary endpoint is median progression-free survival (PFS).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

First-line Anti-PD-1 Therapy Plus Chemotherapy With or Without Radiotherapy in Metastatic Esophageal Squamous Cell Carcinoma: A Phase II Multi-center, Randomized Trial (SCR-ESCC-01)

Actual Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2026

Anticipated Study Completion Date :

Jan 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A PD-1 inhibitor + Paclitaxel + Cisplatin/Carboplatin+ Low-dose radiotherapy (LDRT) + Conventionally fractionated radiotherapy (CFRT)	Radiation: LDRT+CFRT LDRT: Primary tumor and all visible metastatic lesions, DT: 2Gy/2fx, d1-2, Q3W × 4 cycles ; CFRT: Primary tumor, DT:40-50Gy/20-25fx, starting from the 5th immunotherapy cycle Drug: Immunotherapy PD-1 inhibitor 200mg, Q3W, until disease progression or unacceptable toxicity or treatment reaches 2 years Drug: Chemotherapy Paclitaxel+ Cisplatin, Q3W × 4cycles or Paclitaxel+ Carboplatin, Q3W × 4 cycles
Active Comparator: Arm B PD-1 inhibitor + Paclitaxel + Cisplatin/Carboplatin	Drug: Immunotherapy PD-1 inhibitor 200mg, Q3W, until disease progression or unacceptable toxicity or treatment reaches 2 years Drug: Chemotherapy Paclitaxel+ Cisplatin, Q3W × 4cycles or Paclitaxel+ Carboplatin, Q3W × 4 cycles

Arm

Intervention/Treatment

Experimental: Arm A

PD-1 inhibitor + Paclitaxel + Cisplatin/Carboplatin+ Low-dose radiotherapy (LDRT) + Conventionally fractionated radiotherapy (CFRT)

Radiation: LDRT+CFRT

LDRT: Primary tumor and all visible metastatic lesions, DT: 2Gy/2fx, d1-2, Q3W × 4 cycles ; CFRT: Primary tumor, DT:40-50Gy/20-25fx, starting from the 5th immunotherapy cycle

Drug: Immunotherapy

PD-1 inhibitor 200mg, Q3W, until disease progression or unacceptable toxicity or treatment reaches 2 years

Drug: Chemotherapy

Paclitaxel+ Cisplatin, Q3W × 4cycles or Paclitaxel+ Carboplatin, Q3W × 4 cycles

Active Comparator: Arm B

PD-1 inhibitor + Paclitaxel + Cisplatin/Carboplatin

Drug: Immunotherapy

PD-1 inhibitor 200mg, Q3W, until disease progression or unacceptable toxicity or treatment reaches 2 years

Drug: Chemotherapy

Paclitaxel+ Cisplatin, Q3W × 4cycles or Paclitaxel+ Carboplatin, Q3W × 4 cycles

Outcome Measures

Primary Outcome Measures

PFS [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months]
Progression-free survival

Secondary Outcome Measures

OS [From date of randomization until the date of death from any cause, assessed up to 36 months]
Median overall survival
Incidence of Grade III and higher treatment-related adverse events [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18;
Metastatic esophageal squamous cell carcinoma (stage IVB, M1) confirmed by pathology;
ECOG performance status: 0-1 point;
No prior anti-tumor treatment;
Adequate hematologic, renal, hepatic, and cardiac functions that meet the requirements for chemotherapy and immunotherapy assessed by investigators.

Exclusion Criteria:

Non-squamous cell esophageal carcinoma or ESCC mixed with other pathological types of esophageal cancer;
Patients who are potentially curable with surgery as assessed by investigators;
Pleural metastasis or malignant pleural effusion, pericardial effusion;
Any prior anti-tumor therapy for esophageal cancer, i.e., surgery, radiotherapy, chemotherapy, or immunotherapy;
High risk of gastrointestinal bleeding, esophageal fistula, or perforation;
Patients with Patient-Generated Subjective Globe Assessment (PG-SGA) score≥9;
Unstable cardiac diseases or symptoms;
History of interstitial pulmonary disease, non-infectious pneumonitis; pulmonary fibrosis, or other uncontrolled acute pulmonary disease;
Active autoimmune disease or history of autoimmune disease;
Conditions of immunodeficiency or active infection requiring systemic therapy;
Pregnant or breastfeeding;
Patients with synchronous second primary cancer and a history of malignancy within the past 5 years (excluding completely cured cervical carcinoma in situ or basal cell or squamous cell skin carcinoma).