A Phase II Trial of Combination of Toripalimab and Definitive Chemoradiotherapy in Esophageal Squamous Cell Carcinoma

Mian XI1 site in 1 country42 target enrollmentJune 25, 2019

Overview

Brief Summary

Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable esophageal cancer (EC). However, as high as more than 40% of EC patients experienced locoregional recurrence after concurrent CRT. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. The aim of this study was to evaluate the efficacy and safety of the combination of toripalimab (an anti-PD-1 antibody) combined with definitive CRT in locally advanced esophageal squamous cell carcinoma (ESCC).

Registry

clinicaltrials.gov

Start Date

June 25, 2019

End Date

July 31, 2022

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Mian XI

Responsible Party

Sponsor Investigator

Principal Investigator

Mian XI

Associate professor

Sun Yat-sen University

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed squamous cell carcinoma of the esophagus;
•Absence of hematogenous metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan (according to UICC TNM version 8);
•Not suitable for surgery (either for medical reasons or patient's choice);
•Age at diagnosis 18 to 70 years;
•No prior cancer therapy;
•Estimated life expectancy \>6 months;
•Eastern Cooperative Oncology Group performance status ≤ 2
•No history of concomitant or previous malignancy;
•The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥ 4.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L; b. platelets ≥ 100×109/L; c. hemoglobin ≥ 9g/dL; d. serum albumin ≥ 2.8g/dL; e. total bilirubin ≤ 1.5×ULN, ALT, AST and/or AKP ≤ 2.5×ULN; f. serum creatinine ≤ 1.5×ULN or creatinine clearance rate \>60 mL/min;
•Ability to understand the study and sign informed consent.

Exclusion Criteria

•Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
•Patients with hematogenous metastasis disease at diagnosis;
•Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
•Patients who have a preexisting or coexisting bleeding disorder;
•Female patients who are pregnant or lactating;
•Inability to provide informed consent due to psychological, familial, social and other factors;
•Presence of CTC grade ≥ 3 peripheral neuropathy;
•A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
•A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
•Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.

Arms & Interventions

PD-1 group

All patients will receive standard fractionation radiation therapy (RT) scheme: 50.4 Gy in 28 fractions over 5-6 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and 2 cycles of toripalimab 240 mg on days 1, 22 followed by a maintenance phase of toripalimab IV 240 mg every 3 weeks for up to 1 year.

Intervention: Toripalimab

PD-1 group

All patients will receive standard fractionation radiation therapy (RT) scheme: 50.4 Gy in 28 fractions over 5-6 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and 2 cycles of toripalimab 240 mg on days 1, 22 followed by a maintenance phase of toripalimab IV 240 mg every 3 weeks for up to 1 year.

Intervention: Paclitaxel/Cisplatin

PD-1 group

All patients will receive standard fractionation radiation therapy (RT) scheme: 50.4 Gy in 28 fractions over 5-6 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and 2 cycles of toripalimab 240 mg on days 1, 22 followed by a maintenance phase of toripalimab IV 240 mg every 3 weeks for up to 1 year.

Intervention: Intensity-modulated radiotherapy

Outcomes

Primary Outcomes

clinical complete response rate

Time Frame: 3 months after chemoradiotherapy (plus or minus 14 days)

Tumor response was evaluated 3 months after the completion of chemoradiotherapy based on CT or PET-CT scans, endoscopy with biopsies.

Secondary Outcomes

2-year overall survival(From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 24 months)
2-year progression-free survival(From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months)
Incidence of treatment-related adverse events as assessed by CTCAE v4.0(From the start of treatment to 2 year after the completion of treatment)
Duration of response(From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 24 months)