Fraction Dose Escalation of Split-course Hypofractionated Concurrent Chemoradiotherapy Following Induction Chemo-immunotherapy in Unresectable Locally Advanced Esophageal Squamous Carcinoma: a Phase I Study.

Sun Yat-sen University

Status and phase: Active, not recruiting; Phase 1

Conditions: Esophageal Squamous Cell Carcinoma

Treatments: Drug: Concurrent chemotherapy; Drug: Induction chemo-immunotherapy; Radiation: Split-course hypo-CCRT

Study type: Interventional

Funder types: Other

Identifiers

NCT06020885

GASTO-10102

Details and patient eligibility

About

This Phase I study is to determine the maximum tolerated fraction dose (MTD) for split-course hypo-CCRT following induction chemo-immunotherapy in LA-ESCC patients, to clarify the dosimetric advantage of split-course hypo-CCRT, and to investigate the treatment-related toxicities and quality of life of the new regimen.

Full description

This Phase I study is to determine the maximum tolerated fraction dose (MTD) for split-course hypo-CCRT following induction chemo-immunotherapy in LA-ESCC patients, to clarify the dosimetric advantage of split-course hypo-CCRT, and to investigate the treatment-related toxicities and quality of life of the new regimen.

Enrollment: 18 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• histologically confirmed ESCC
• II-IVB stages (IVB stage only with metastatic celiac or supraclavicular lymph nodes) based on the TNM staging system proposed by the International Union Against Cancer (UICC 2002)
• Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
• Charlson Comorbidity Index score≤4
• oral medication can be administered despite esophageal obstruction
• adequate hematological, renal and hepatic functions

Exclusion criteria

• contraindication for radiotherapy or chemotherapy
• prior malignancies, except for curable non-melanoma skin cancer or cervical carcinoma in situ
• distant metastasis, except for celiac or supraclavicular lymph nodes metastases

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

18 participants in 1 patient group

Experiment group

Experimental group

Description:

This is a prospective, single-arm, phase 1 trial. A total of 18 unresectable LA-ESCC patients are required to be enrolled. 1. Induction chemo-immunotherapy All patients receive 2-3 cycles of Abraxane 260mg/m2 d1+cisplatin 60mg/m2 d1+Toripalimab 240mg d1. 2. Hypo-CCRT Evaluation will be performed three weeks after the induction chemo-immunotherapy, LA-ESCC patients without disease progression will continue the split-course hypo-CCRT treatment. Split-course hypo-CCRT is administered at the following three dose levels: * Level 1: DT 3000cGy/10 daily fractions/300cGy in the first course, DT 2000cGy/10 daily fractions/200cGy in the second course; * Level 2: DT 2800cGy/7 daily fractions/400cGy in the first course, DT 2200cGy/10 daily fractions/220cGy in the second course; * Level 3: DT 2500cGy/5 daily fractions/500cGy in the first course, DT 2500cGy10 daily fractions/250cGy in the second course.

Treatment:

Radiation: Split-course hypo-CCRT

Drug: Induction chemo-immunotherapy

Drug: Concurrent chemotherapy