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

• Sponsor: Sun Yat-sen University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05357846
• Collaborator: Affiliated Cancer Hospital of Shantou University Medical College (Other)
• Enrollment: 422
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 103
• Patients Per Site Per Month: 4.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Esophageal Carcinoma; Esophageal Cancer; Oesophageal Cancer	Drug: Sintilimab; Radiation: Preoperative radiotherapy; Drug: Paclitaxel; Drug: Cisplatin; Procedure: esophagectomy	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 422 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Multicenter Randomized Controlled Trial of PD-1 Inhibitor Combined With Preoperative Concurrent Chemoradiotherapy and Surgery for Locally Advanced Esophageal Squamous Cell Carcinoma
• Anticipated Study Start Date: Jun 1, 2022
• Anticipated Primary Completion Date: Jan 1, 2031
• Anticipated Study Completion Date: Jan 1, 2031

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Sintilimab; Sintilimab 200mg, IV (in the vein) on day 1 and day 22; Radiation: Preoperative radiotherapy; External radiation with a total dose of 40.0 or 45.0 Gy is given in 20 fractions,5 fractions a week.; Drug: Paclitaxel; 50mg/m2, IV (in the vein) on day 1,day 8,day 15 and day 22; Other Names: Taxol ; Drug: Cisplatin; 25mg/m2,IV DRIP on day 1,day 8,day 15 and day 22; Other Names: DDP ; Procedure: esophagectomy; McKeown esophagectomy, Ivor Lewis esophagectomy or minimally invasive esophagectomy will be performed 6-8 weeks after chemoradiotherapy. Two-field lymphadenectomy with total mediastinal lymph node dissection is performed during surgery.
Active Comparator: 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	Radiation: Preoperative radiotherapy; External radiation with a total dose of 40.0 or 45.0 Gy is given in 20 fractions,5 fractions a week.; Drug: Paclitaxel; 50mg/m2, IV (in the vein) on day 1,day 8,day 15 and day 22; Other Names: Taxol ; Drug: Cisplatin; 25mg/m2,IV DRIP on day 1,day 8,day 15 and day 22; Other Names: DDP ; Procedure: esophagectomy; McKeown esophagectomy, Ivor Lewis esophagectomy or minimally invasive esophagectomy will be performed 6-8 weeks after chemoradiotherapy. Two-field lymphadenectomy with total mediastinal lymph node dissection is performed during surgery.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. Pathologic complete response rate [Two weeks after surgery]

   No malignant tumor cells were detected in the removed specimens including primary tumor and lymph nodes

3. R0 resection rate [Two weeks after surgery]

   The percentage of patients who undergo complete resection

4. Incidence of perioperative complications [Ninety days after surgery]

   Incidence of complications

5. Perioperative mortality [Ninety after surgery]

   Incidence of death postoperatively

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 ).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China	510060

Sponsors and Collaborators

• Sun Yat-sen University
• Affiliated Cancer Hospital of Shantou University Medical College

Investigators

• Principal Investigator: HONG YANG, Sun Yat-sen University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yang Hong, Prof., Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT05357846
• Other Study ID Numbers: NEOCRTEC2101
• First Posted: May 3, 2022
• Last Update Posted: May 3, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Esophageal Neoplasms; Paclitaxel; Cisplatin

Study Results

No Results Posted as of May 3, 2022