Phase III Multicenter Randomized Controlled Trial of PD-1 Inhibitor Combined With Preoperative Concurrent Chemoradiotherapy and Surgery for Locally Advanced Esophageal Squamous Cell Carcinoma (NEOCRTEC2101)
Overview
- Phase
- Phase 3
- Intervention
- Sintilimab
- Conditions
- Squamous Cell Esophageal Carcinoma
- Sponsor
- Sun Yat-sen University
- Enrollment
- 422
- Locations
- 1
- Primary Endpoint
- Overall survival
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
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.
Investigators
Yang Hong
Prof.
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage T1-4aN1-3M0 or T3-4aN0M0,which is potentially resectable.
- •Patients must not have received any prior anticancer therapy.
- •More than 6 months of expected survival.
- •Age ranges from 18 to 70 years.
- •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.
- •WHO PS score 0-1
- •Signed informed consent document on file.
Exclusion Criteria
- •Patients have received any prior anticancer therapy.
- •Patients are diagnosed or suspected to be allergic to sintilimab,toxal or cisplatin.
- •Patients with concomitant hemorrhagic disease.
- •Patients who cannot tolerate surgery.
- •Pregnant or breast feeding.
- •Patients without informed consent because of psychological, family, social or any other factors.
- •Patients with concomitant peripheral neuropathy, whose CTC status is 2 or even more.
- •Patients with malignant tumors other than esophageal cancer,except for non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer.
- •Patients with history of diabetes over 10 years and unsatisfactory glycemic control.
- •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.
Arms & Interventions
NCRT+IO group
• 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
Intervention: Sintilimab
NCRT+IO group
• 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
Intervention: Preoperative radiotherapy
NCRT+IO group
• 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
Intervention: Paclitaxel
NCRT+IO group
• 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
Intervention: Cisplatin
NCRT group
• 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
Intervention: Paclitaxel
NCRT+IO group
• 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
Intervention: esophagectomy
NCRT group
• 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
Intervention: Preoperative radiotherapy
NCRT group
• 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
Intervention: Cisplatin
NCRT group
• 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
Intervention: esophagectomy
Outcomes
Primary Outcomes
Overall survival
Time Frame: 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 Outcomes
- Perioperative mortality(Ninety after surgery)
- Progression free survival(At end of enrollment- up to 5 years in follow up)
- Pathologic complete response rate(Two weeks after surgery)
- Incidence of perioperative complications(Ninety days after surgery)
- R0 resection rate(Two weeks after surgery)