A Clinical Study on the Efficacy and Safety of Paclitaxel Polymer Micelles and Cisplatin Combined With Cadonilimab as a Neoadjuvant Therapy for Locally Advanced Esophageal Squamous Cell Carcinoma

Neoadjuvant Therapy Clinical Trial

Official title:

A Clinical Study on the Efficacy and Safety of Paclitaxel Polymer Micelles and Cisplatin Combined With Cadonilimab as a Neoadjuvant Therapy for Locally Advanced Esophageal Squamous Cell Carcinoma：A Single Arm, Single Center, Prospective Clinical Trial (POINTS Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06356688
• Other study ID #: 13914704178
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 20, 2024
• Est. completion date: June 20, 2025

Study information

• Verified date: April 2024
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Jing Sun
• Phone: 13914704178
• Email: sunj[@]njmu.edu.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the efficacy and safety of neoadjuvant treatment of locally advanced esophageal squamous carcinoma with a PD-1/CTLA-4 bispecific antibody (cadonilimab) in combination with platinum-containing chemotherapy (paclitaxel polymer micelles combined with cisplatin). Includes pathologic complete remission rates (pCR rates) after 2-4 cycles of cadonilimab combination chemotherapy. The objective remission rate (ORR), major pathologic remission rate (MPR), R0 resection rate and 2-year overall survival (OS) and progression-free survival (OS) rates, and safety of neoadjuvant treatment of locally advanced esophageal squamous carcinoma with cadonilimab combined with chemotherapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: June 20, 2025
• Est. primary completion date: April 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age =18 years, =75 years, gender is not limited;

2. Squamous esophageal cancer of thoracic segment confirmed by pathology;

3. Locally advanced patients with no distant metastasis by imaging, resectable or potentially resectable after discussion among oncology, esophageal surgery, and imaging, and clinical stage cT2-4aN+ or cT3-4aN0, M0, stage II, III, or IVA (AJCC 8th edition cTNM staging);

4. ECOG PS score of 0-1;

5. No previous antitumor treatment such as radiotherapy, chemotherapy and immunotherapy;

6. Expected survival > 6 months;

7. Adequate baseline organ function: (i) WBC =3×10^9/L, ANC =1.5×10^9/L, PLT =100×10^9/L, Hb =9g/dL; (ii) Liver function: TBIL =2ULN, AST =2.5ULN, ALT =2.5ULN; (iii) Renal function: cCr>40 ml/min, Cr=1.5 ULN; (iv) Cardiac function: no cardiac disease or coronary artery disease. Cardiac function: no heart disease or coronary heart disease, patients with cardiac function grade 1-2;

8. Hypertensive patients applying antihypertensive drugs to control blood pressure within the normal range;

9. Diabetic patients with fasting blood glucose controlled at =8mmol/L by hypoglycemic drug treatment;

10. No other serious diseases (such as autoimmune diseases, immunodeficiency, organ transplantation, or other diseases that require continuous hormone therapy) that conflict with this protocol;

11. No history of other malignant tumors;

12. The patient agrees to participate in this clinical study and signs the Informed Consent Form.

Exclusion Criteria:

1. Patients who have previously received anti-tumor therapy (including chemotherapy, radiotherapy, surgery or immunotherapy, etc.);

2. Combination of other incurable malignant tumors (except cured non-malignant skin tumors, cervical cancer in situ, and prostate cancer);

3. Patient has or anticipates a significant risk of esophageal perforation, fistula, and hemorrhage;

4. Active autoimmune or immunodeficiency disease, use of immunosuppressants prior to enrollment, and use of immunosuppressant dosage =10 mg/day of oral prednisone for more than 2 weeks;

5. Clinically significant cardiovascular disease including, but not limited to, severe acute myocardial infarction, unstable or severe angina pectoris, coronary artery bypass grafting surgery, congestive heart failure, ventricular arrhythmia requiring medical intervention, left ventricular ejection fraction <50%, or other anticipated inability to tolerate chemoradiotherapy in the 6 months prior to enrollment;

6. Severe allergies;

7. Pregnant or lactating women;

8. Severe mental disorders;

9. Presence of CTC grade =3 peripheral nerve disease;

10. Abnormal coagulation function (PT > 16s, APTT > 53s, TT > 21s, Fib < 1.5g/L), bleeding tendency or undergoing thrombolytic or anticoagulant therapy;

11. Presence of severe pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, severe impairment of lung function, or active tuberculosis within 1 year;

12. Presence of active hepatitis B or C;

13. Any other condition that the investigator evaluates to be ineligible for enrollment.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Locally Advanced Esophageal Squamous Cell Carcinoma
• Neoadjuvant Therapy

Intervention

Drug:
• paclitaxel polymer micelles and cisplatin combined with Cadonilimab
Paclitaxel polymer micelles:Cycle 1: 230mg/m2, IV =3 hours; Cycles 2-4: If the patient has a neutrophil nadir =1.0 x 109/L along with a platelet nadir =80 x 109/L after Cycle 1 dosing and has not experienced grade II-IV non-hematologic toxicity, then give 260mg/m2, IV =3 hours, d1, q3w; Cisplatin: 25mg/m2/d x d1-3, IV drip, q3w; Cadonilimab: 375mg, IV drip, d3, q3w;

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sun Jing

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response (pCR) rates	evaluate pathological complete response rate of primary tumor and locally metastatic lymph nodes after 2-4 cycles of neoadjuvant therapy.	From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
Secondary	Objective Rate of Effectiveness (ORR)	the proportion of patients who achieve PR or CR	From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
Secondary	R0 Removal Rate	Rate of microscopically margin-negative resection	From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
Secondary	2-year overall survival rate	2-year overall survival rate	2 years
Secondary	2-year disease free survival rate	2-year disease free survival rate	2 years
Secondary	major pathological response (MPR)		From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.