Efficacy and Safety of Preoperative Sintilimab Plus Nab-paclitaxel and Cisplatin in BR-ESCC Patients

NCT ID: NCT04548440

Last Updated: 2025-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-31
• Study Completion Date: 2022-12-31

Brief Summary

An open-label, non-randomized, phase II study to assess the safety and efficacy of Preoperative Sintilimab Plus Nab-paclitaxel and Cisplatin in Borderline Resectable Esophageal Squamous Cell Carcinoma patients

Detailed Description

PRIMARY OBJECTIVES:

To determine the R0 resection rate of Borderline Resectable Esophageal Squamous Cell Carcinoma patients who used preoperative Sintilimab Plus Nab-paclitaxel and Cisplatin

SECONDARY OBJECTIVES:

To evaluate the Pathological Complete Response (pCR) rate, Progression Free Survival (PFS), Relapse Rate, Tumor Regression Grading (TRG) post preoperative chemotherapy, Overall Survival (OS), safety and toxicity of chemotherapy regimen and surgery.

EXPLORATORY OBJECTIVES:

Exploring the benefits of this treatment strategy in Borderline Resectable Esophageal Squamous Cell Carcinoma patients at a molecular level

OUTLINE:

Eligible patients receive Sintilimab and cisplatin intravenously on day 1 and albumin-bound paclitaxel intravenously on days 1 and 8. This cycle is repeated every 3 weeks in the absence of disease progression or unacceptable toxicity. Radiological and multidisciplinary assessment is performed after every 2-4 cycles.

Conditions

Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Preoperative Sintilimab plus Nab-paclitaxel and Cisplatin

Patients receive the following regimen every 3 weeks:

Sintilimab 200mg IV on Day 1; Albumin-bound paclitaxel 125 mg/m2 IV on Day 1 and Day 8; Cisplatin 75mg/m2 IV on Day 1; Standard hydration regimen on Day 0-3

After 2-4 cycles, radiological evaluation and multidisciplinary assessment will be performed. If radical resection is possible, surgery is to be performed 3-6 weeks after the last chemotherapy session. In the case of a R0 resection, the investigator will decide whether to perform adjuvant therapy depending on the patient's condition; in the case of R1 or R2 resection, concurrent chemoradiotherapy is recommended. If the multidisciplinary assessment considers that radical resection is not possible, radical concurrent chemoradiotherapy is performed.

Group Type: EXPERIMENTAL

Sintilimab

Intervention Type: DRUG

Route of administration: Intravenous

Nab paclitaxel

Intervention Type: DRUG

Route of administration: Intravenously over 30min

Cisplatin

Intervention Type: DRUG

Route of administration: Intravenous

Interventions

Sintilimab

Route of administration: Intravenous

Intervention Type: DRUG

Nab paclitaxel

Route of administration: Intravenously over 30min

Intervention Type: DRUG

Cisplatin

Route of administration: Intravenous

Intervention Type: DRUG

Other Intervention Names

Anti-PDCD1 monoclonal antibody IBI308; Tyvyt; Nanoparticle Albumin-Bound Paclitaxel; Abraxane; CDDP; Platinol

Eligibility Criteria

Inclusion Criteria

1. Patients must provide a signed Informed Consent Form

2. Age ≥18 years old

3. Histological confirmation of T4N0-3M0 thoracic esophageal squamous cell carcinoma, absence of distant metastasis and confirmation of a borderline resectable lesion after multidisciplinary assessment using enhanced CT and/or Endoscopic Esophageal Ultrasound or Endobronchial Ultrasound. The definition of a borderline resectable lesion includes: CT showing that the fat gap between the tumor and the aorta is blurred, the angle between three contiguous planes (2mm/layer) and the aorta exceeds 90 degrees; or Endoscopic Esophageal Ultrasound revealing that the tumor has invaded the adventitia layer of the esophagus, and the boundary with the aorta is unclear; or Endobronchial Ultrasound showing an unclear border between the tumor and trachea or bronchus, but has yet invaded the trachea or bronchial mucosa or submucosa

4. Patients have not received any anti-tumor treatment for esophageal cancer (including surgery, chemotherapy, interventional therapy, immunotherapy, radiotherapy, etc.)

5. Life expectancy ≥3 months

6. General physical status (ECOG PS score) 0-1 points

7. Blood routine test (within 7 days): Hb ≥9g/L, NE ≥1.5×109/L, PLT ≥90×109/L

8. Liver and kidney function test (within 7 days): total bilirubin ≤1.5 UNL, creatinine ≤1.5× UNL, AST /ALT ≤2.5xUNL, ALP ≤5.0xUNL

9. No serious complications such as active gastrointestinal bleeding, perforation, jaundice, intestinal obstruction, fever unrelated to malignant disease>38℃

10. Patients with reproductive potential should take effective contraceptive measures

11. Patients with good compliance and that can attend scheduled follow up to assess the efficacy and adverse reactions of the treatment

Exclusion Criteria

1. Patients with cervical esophageal squamous cell carcinoma

2. Patients with distant metastases

3. Patients with a high risk of complete esophageal obstruction and require interventional therapy

4. Patients with stent implantation in the esophagus or trachea

5. Patients with an esophageal tumor that invaded adjacent organs (aorta or trachea), causing an increased risk of bleeding or perforation, or patients with a fistula

6. Concurrent primary cancers (except for cured skin basal cell carcinoma and cervical carcinoma in situ)

7. History of immunosuppressive drug use within 1 week before treatment, excluding nasal spray, inhalation or use of local glucocorticoids or physiological doses of systemic glucocorticoids (not exceeding 10 mg/day prednisone or equivalent doses of other glucocorticoids) or glucocorticoids used to prevent contrast agent allergy.

8. Patients with active or a past history (within 2 years) of autoimmune disease that need symptomatic treatment (Patient diagnosed with vitiligo, psoriasis, alopecia, or Grave disease that did not require systemic treatment within the past 2 years, hypothyroidism that requires only thyroid hormone replacement therapy and type I diabetes patients treated with insulin replacement therapy only are eligible)

9. Patients with a history of primary immunodeficiency disease

10. Patients with a history of active tuberculosis

11. Patients with a past history of allogenic organ transplantation and allogeneic hematopoietic stem cell transplantation

12. Patients diagnosed with interstitial lung disease that require steroid therapy

13. Patients with a known history of allergy to any monoclonal antibody or chemotherapeutic drugs (taxanes, cisplatin) or their constituents.

14. Patients with a history of severe heart disease, including: history of congestive heart failure, patients with high-risk of uncontrolled arrhythmias, angina pectoris requiring medical treatment, clinically diagnosed heart valve disease, history of severe myocardial infarction and refractory hypertension

15. Patients with chronic diarrhea (4 or more watery stools per day) and patient with renal insufficiency

16. Patients with an active infection or an active infectious disease

17. Neurological or mental disorders that affect cognitive ability

18. Pregnant or breastfeeding women

19. Other acute or chronic diseases, mental diseases or laboratory test values that may cause the following abnormal outcomes: Increase participants or drug administration related risks, interfere with the interpretation of the study results, and patients deemed as ineligible to participate in the study based on the investigator's judgment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innovent Biologics (Suzhou) Co. Ltd.

INDUSTRY

Sponsor Role: collaborator

CSPC Pharmaceutical Group Limited

INDUSTRY

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Yuhong Li

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yuhong Li, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

Other Identifiers

BRESCC-Preoperative 02

Identifier Type: -

Identifier Source: org_study_id