A Study of Sintilimab Plus Chemoradiation Before Surgery for Esophageal Cancer

Early Phase 1

• Conditions: Esophageal Squamous Cell Carcinoma
• Interventions: Biological: Sintilimab; Drug: carboplatin/paclitaxel; Radiation: Radiation

• Registration Number: NCT03940001
• Lead Sponsor: Zhejiang Cancer Hospital

Brief Summary

The purpose of this study is to test the the efficacy and safety of sintilimab in combination with chemoradiation before surgery for esophageal cancer.

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-05
• Study Start: 2019-05-01
• Study First Submitted: 2019-05-04
• Study First Submitted QC: 2019-05-04
• Study First Posted: 2019-05-07
• Last Update Submitted: 2019-09-05
• Last Update Posted: 2019-09-09
• Primary Completion: 2021-05-01
• Study Completion: 2022-05-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Histologically or cytologically confirmed esophageal squamous carcinoma
• 18≤age≤75
• ECOG PS is 0-1
• TanyN+M0 or T3-4NanyM0 tumors
• Patients must have surgically resectable disease treatable by esophagectomy, as assessed by a thoracic surgeon
• No prior chemotherapy,radiotherapy and immunotherapy
• Disease must be clinically limited to the esophagus
• No esophageal perforation and no active esophageal bleeding
• No interstitial pneumonia or history of interstitial pneumonia
• FEV1>1.2L
• Adequate organ function defined at baseline as: WBC ≥3,000/ L，ANC ≥1,500/ L，Platelets ≥100,000/ L，Hb ≥9 g/dl； Calculated creatinine clearance >40 ml/min using Cockcroft-Gault method: Males: Creatinine CL = Weight (kg) x (140 - Age) . (mL/min) 72 x serum creatinine (mg/dL)Female：Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)；Total serum bilirubin ≤1.5 mg/dL， AST/ALT ≤2.5× upper limit of normal，Mean QT interval corrected for heart rate (QTc) <470 ms calculated from 3 ECGs using Frediricia's Correction
• Able to provide written informed consent
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Exclusion Criteria

• Previous treatment with chemotherapy, radiotherapy or immunotherapy
• Cervical esophageal cancer
• Esophageal perforation or active esophageal bleeding
• Interstitial pneumonia or history of interstitial pneumonia
• Patients with evidence of metastatic disease
• Chronic Hepatitis B or C infection (e.g. Hepatitis B surface Ag positive or detectable viral load for Hepatitis B or C). Patients with prior evidence of Hepatitis B or C without active infection are eligible
• Autoimmune diseases (such as systemic lupus erythematosus, rheumatoid rthritis, inflammatory bowel disease, autoimmune thyroid disease), but allow the following diseases to enter the next stage of screening: type I diabetes, skin diseases without systemic treatment (such as vitiligo, psoriasis)
• 14 days before the first dose, the patient had an active infection that required systemic treatment
• Inability to understand or may not comply with test requirements

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
arm	Sintilimab	Biological: Sintilimab For weight \<60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1 Drug: Paclitaxel 50 mg/m\^2 IV Q3W day 1, day 8 and day 15 Drug: carboplatin AUC: 2 IV Q3W day 1, day 8 and day 15 Radiotherapy: 1.8 Gy/fraction ×23 fractions Monday to Friday total dose of 41.4 Gy
arm	carboplatin/paclitaxel	Biological: Sintilimab For weight \<60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1 Drug: Paclitaxel 50 mg/m\^2 IV Q3W day 1, day 8 and day 15 Drug: carboplatin AUC: 2 IV Q3W day 1, day 8 and day 15 Radiotherapy: 1.8 Gy/fraction ×23 fractions Monday to Friday total dose of 41.4 Gy
arm	Radiation	Biological: Sintilimab For weight \<60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1 Drug: Paclitaxel 50 mg/m\^2 IV Q3W day 1, day 8 and day 15 Drug: carboplatin AUC: 2 IV Q3W day 1, day 8 and day 15 Radiotherapy: 1.8 Gy/fraction ×23 fractions Monday to Friday total dose of 41.4 Gy

Primary Outcome Measures

Name	Time	Method
unacceptable toxicity	1 year	"Unacceptable toxicity" is defined as any of the following toxicities: \>1 episode of grade 3/4 neutropenia or thrombocytopenia \<75,000/μL (despite prior dose reduction) during chemoradiation any toxicity that results in \>2 week cumulative delay in chemoradiation any toxicity that is attributed to durvalumab which results in a delay of \>8 weeks in surgery, i.e. surgery \>16 weeks from the end of radiation, for a potentially operable patient any reason that is attributed to durvalumab which leads to death within 30 days of surgery
pathologic complete response rate, pCR	1 year
major pahological response, MPR	1 year

Trial Locations

Locations (1)

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China