PD-1 Inhibitor Combined With Neoadjuvant Chemoradiotherapy Plus Surgery for Locally Advanced ESCC (NEOCRTEC2101)

Phase 3

Recruiting

• Conditions: Squamous Cell Esophageal Carcinoma; Esophageal Cancer; Oesophageal Cancer
• Interventions: Drug: Sintilimab; Radiation: Preoperative radiotherapy; Drug: Paclitaxel; Drug: Cisplatin; Procedure: esophagectomy

• Registration Number: NCT05357846
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The primary objective is to compare PD-1 inhibitor combined with preoperative chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery, in terms of the overall survival time (OS) in patients with Stage T1-4aN1-3M0 or T3-4aN0M0 squamous cell esophageal carcinoma.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-03-22
• Study First Submitted QC: 2022-05-01
• Study First Posted: 2022-05-03
• Study Start: 2022-11-01
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-11
• Last Update Posted: 2024-01-16
• Primary Completion: 2031-01
• Study Completion: 2031-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 422

Inclusion Criteria

1. Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage T1-4aN1-3M0 or T3-4aN0M0,which is potentially resectable.
2. Patients must not have received any prior anticancer therapy.
3. More than 6 months of expected survival.
4. Age ranges from 18 to 70 years.
5. Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney.
6. WHO PS score 0-1
7. Signed informed consent document on file.

Exclusion Criteria

1. Patients have received any prior anticancer therapy.
2. Patients are diagnosed or suspected to be allergic to sintilimab,toxal or cisplatin.
3. Patients with concomitant hemorrhagic disease.
4. Patients who cannot tolerate surgery.
5. Pregnant or breast feeding.
6. Patients without informed consent because of psychological, family, social or any other factors.
7. Patients with concomitant peripheral neuropathy, whose CTC status is 2 or even more.
8. Patients with malignant tumors other than esophageal cancer,except for non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer.
9. Patients with history of diabetes over 10 years and unsatisfactory glycemic control.
10. Patients with severe heart,lung,liver,renal dysfunction, hematopoietic system diseases, immune system diseases, cachexia or other diseases that lead to intolerance of chemoradiotherapy or surgery.
11. Patients with history of autoimmune diseases, immunodeficiency, or organ and allogeneic bone marrow transplantation.
12. Patients with history of interstitial lung disease or noninfectious pneumonia.
13. Patients with active pulmonary tuberculosis infection, or a history of active pulmonary tuberculosis infection within one year before enrollment, or a history of active pulmonary tuberculosis infection more than one year ago without regular treatment.
14. Patients with active hepatitis B ( HBV DNA ≥ 2000 IU / mL or 104 copies / mL ) or hepatitis C ( HCV antibody positive ).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NCRT+IO group	Sintilimab	• NCRT+IO group consists of the PD-1 inhibitor combined with concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks.PD-1 inhibitor is given by intravenous infusion on days 1 and 22. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: * Radiation: (40 or 45 Gy/20 fractions) * Drug: Sintilimab * Drug: Paclitaxel * Drug: Cisplatin
NCRT+IO group	Preoperative radiotherapy	• NCRT+IO group consists of the PD-1 inhibitor combined with concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks.PD-1 inhibitor is given by intravenous infusion on days 1 and 22. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: * Radiation: (40 or 45 Gy/20 fractions) * Drug: Sintilimab * Drug: Paclitaxel * Drug: Cisplatin
NCRT+IO group	esophagectomy	• NCRT+IO group consists of the PD-1 inhibitor combined with concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks.PD-1 inhibitor is given by intravenous infusion on days 1 and 22. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: * Radiation: (40 or 45 Gy/20 fractions) * Drug: Sintilimab * Drug: Paclitaxel * Drug: Cisplatin
NCRT+IO group	Paclitaxel	• NCRT+IO group consists of the PD-1 inhibitor combined with concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks.PD-1 inhibitor is given by intravenous infusion on days 1 and 22. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: * Radiation: (40 or 45 Gy/20 fractions) * Drug: Sintilimab * Drug: Paclitaxel * Drug: Cisplatin
NCRT+IO group	Cisplatin	• NCRT+IO group consists of the PD-1 inhibitor combined with concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks.PD-1 inhibitor is given by intravenous infusion on days 1 and 22. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: * Radiation: (40 or 45 Gy/20 fractions) * Drug: Sintilimab * Drug: Paclitaxel * Drug: Cisplatin
NCRT group	Preoperative radiotherapy	• NCRT group consists of the concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: * Radiation: (40 or 45 Gy/20 fractions) * Drug: Paclitaxel * Drug: Cisplatin
NCRT group	esophagectomy	• NCRT group consists of the concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: * Radiation: (40 or 45 Gy/20 fractions) * Drug: Paclitaxel * Drug: Cisplatin
NCRT group	Cisplatin	• NCRT group consists of the concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: * Radiation: (40 or 45 Gy/20 fractions) * Drug: Paclitaxel * Drug: Cisplatin
NCRT group	Paclitaxel	• NCRT group consists of the concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: * Radiation: (40 or 45 Gy/20 fractions) * Drug: Paclitaxel * Drug: Cisplatin

Primary Outcome Measures

Name	Time	Method
Overall survival	At end of enrollment- up to 5 years in follow up	Overall survival will be calculated from the date of randomization and an event registered on the date of death from any cause. Patients lost to follow up, or those with no death recorded on the day the database is frozen, will be censored on the date of last follow up.

Secondary Outcome Measures

Name	Time	Method
Perioperative mortality	Ninety after surgery	Incidence of death postoperatively
Progression free survival	At end of enrollment- up to 5 years in follow up	Progression free survival is defined as the time from randomization until objective tumor progression or death.
Pathologic complete response rate	Two weeks after surgery	No malignant tumor cells were detected in the removed specimens including primary tumor and lymph nodes
Incidence of perioperative complications	Ninety days after surgery	Incidence of complications
R0 resection rate	Two weeks after surgery	The percentage of patients who undergo complete resection

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China