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

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

A Phase II Clinical Study of the Efficacy and Safety of Preoperative Sintilimab in Combination With Nab-paclitaxel and Cisplatin in Borderline Resectable Esophageal Squamous Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04548440
• Other study ID #: BRESCC-Preoperative 02
• Status: Completed
• Phase: Phase 2
• Start date: August 31, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2023
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Esophageal Squamous Cell Carcinoma

Intervention

Drug:
• Sintilimab
Route of administration: Intravenous
• Nab paclitaxel
Route of administration: Intravenously over 30min
• Cisplatin
Route of administration: Intravenous

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Sun Yat-sen University	CSPC Pharmaceutical Group Limited, Innovent Biologics (Suzhou) Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	R0 resection rate of patients who underwent surgery following preoperative treatment	The proportion of people with a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.	up to 28 weeks
Secondary	Pathological complete response rate of patients who received surgery following preoperative treatment	The proportion of patients showing an absence of invasive/in situ cancer after treatment	up to 28 weeks
Secondary	Progression free survival from the date of first drug administration until the date of first documented progression or date of death, whichever came first.	The length of time during and after the treatment of the disease, that a patient lives with the disease without its aggravation	up to 28 weeks
Secondary	Tumor regression rate of patients following preoperative treatment	A decrease in the size of a tumor or the extent of cancer in the body	immediately before surgery
Secondary	Relapse rate of patients who received surgery following preoperative treatment	The number of people with deterioration or recurrence of cancer after a temporary improvement	up to 28 weeks
Secondary	Overall survival from the date of first drug administration until the date of death from any cause	The length of time from the start of treatment that patients diagnosed are still alive	up to 28 weeks
Secondary	Number of patients with adverse events and severity according to NCI CTCAE v5.0	Summary of the Adverse events experienced during treatment related to the drug used or surgery in this study	up to 28 weeks