A Study of Neoadjuvant Therapy for the Treatment of Patients With Locally Advanced Esophageal Squamous Cell Carcinoma

Official title

Neoadjuvant Immunotherapy Plus Chemotherapy and Anlotinib Versus Immunotherapy Combined With Concurrent Chemoradiotherapy in the Treatment of Locally Advanced ESCC

Overview

The goal of this interventional study is to compare the safety and efficacy of neoadjuvant immunotherapy plus chemotherapy and anlotinib versus immunotherapy combined with concurrent chemoradiotherapy in the treatment of locally advanced esophageal squamous cell carcinoma. The main question it aims to answer is: To evaluate the safety and efficacy of neoadjuvant immunotherapy plus chemotherapy and anlotinib versus immunotherapy combined with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma and to explore the optimal preoperative neoadjuvant treatment regimen for esophageal squamous cell carcinoma.

Detailed description

The goal of this single-center, open-label, non-inferior, randomized controlled, interventional study is to compare the safety and efficacy of neoadjuvant immunotherapy plus chemotherapy and anlotinib versus immunotherapy combined with concurrent chemoradiotherapy in the treatment of locally advanced esophageal squamous cell carcinoma. The main question it aims to answer is: To evaluate the safety and efficacy of neoadjuvant immunotherapy plus chemotherapy and anlotinib versus immunotherapy combined with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma and to explore the optimal preoperative neoadjuvant treatment regimen for esophageal squamous cell carcinoma.

Interventions

• Drug anlotinib
  Drug: Camrelizumab 200mg on Day 1 of each 3-week cycle for 2 cycles during the neoadjuvant period Drug: Carboplatin Area under the curve of 5 on Day 1 of each 3-week cycle for 2 cycles Drug: Cisplatin 75 mg/m2 on Day 1 of each 3-week cycle, for 2 cycles Drug: Paclitaxel 135-175 mg/m2 on Day 1 of each 3-week cycle for 2 cycles Drug: Nab-Paclitaxel 220-260 mg/m2 on Day 1 of each 3-week cycle for 2 cycles Drug: anlotinib 8 mg/day orally (from days 1 to 14 in a 21-day cycle) for 2 cycles
• Radiation Thoracic radiotherapy
  Drug: Camrelizumab 200mg on Day 1 of each 3-week cycle for 2 cycles during the neoadjuvant period Drug: Carboplatin Area under the curve of 5 on Day 1 of each 3-week cycle for 2 cycles Drug: Cisplatin 75 mg/m2 on Day 1 of each 3-week cycle, for 2 cycles Drug: Paclitaxel 135-175 mg/m2 on Day 1 of each 3-week cycle for 2 cycles Drug: Nab-Paclitaxel 220-260 mg/m2 on Day 1 of each 3-week cycle for 2 cycles Thoracic radiotherapy RT once daily (from cycle 1 \[C1D1\], 41.4Gy/23Fx, 1.8Gy daily, for

Primary outcome measures

• Pathological complete response (pCR), Major pathological response (MPR) [Time frame: Up to approximately 15 weeks after randomization]
• Major pathological response (MPR) [Time frame: Up to approximately 15 weeks after randomization]

Secondary outcome measures (4)

• Objective response rate (ORR) [Time frame: Up to approximately 15 weeks after randomization]
• 3-year disease free survival [Time frame: From date of randomization to approximately 3 years after date of resection]
• R0 excision rate [Time frame: Up to approximately 15 weeks after randomization]
• 3-year overall survival [Time frame: From date of randomization to approximately 3 years after date of resection]

Eligibility criteria

Inclusion criteria

• Surgically resectable cT1-4aN+M0 or cT3-4aN0M0 esophageal squamous cell carcinoma initially diagnosed by histology or cytology
• Patients who can take anlotinib capsules orally
• No previous systematic antitumor treatment
• ECOG PS 0-1
• The function of important organs meets the following requirements: absolute neutrophil count≥1.5×10\^9 / L; platelet≥80×10\^9 / L; hemoglobin≥80×10\^9 / L; total bilirubin≤1.5×upper limit of normal; within normal serum creatinine; ALT and glutamatergic aminase≤2.5× upper limit of normal
• No incurable serious complications or other major diseases
• The thoracic surgeon judges that the operation can be tolerated
• Female subjects with fertility, and male subjects with childbearing partners, required a medically approved contraceptive during study treatment and at least 6 months after the last chemotherapy
• The subjects volunteered to join the study, signed informed consent, had good compliance and cooperated with follow-up

Exclusion criteria

• BMI\<18.5kg/m2 or 10% weight loss in 2 months before screening (while considering the effect of large chest ascites on body weight)
• Patients with tracheal / bronchial / macrovascular invasion, deep ulcer esophagus, digestive tract perforation and / or fistula, major bleeding, and poor lung function or previous chronic lung disease within 6 months prior to initial medication
• Patients with significant feeding obstruction unable to take oral anlotinib
• Known history of allergy to any component of biological or PD-1 mab formulation, albumin-bound paclitaxel, carboplatin and other platinum drugs manufactured by Chinese hamster ovary cells (CHO)
• Have received any of the following treatments: any investigational drug; enrolled in another clinical study except for an observational (non-interventional) clinical study; received anti-tumor or live vaccine
• A history of active autoimmune diseases and autoimmune diseases
• A history of immunodeficiency, including a positive HIV test, or other acquired, congenital immunodeficiency disorders, or a history of organ transplantation and allogeneic bone marrow transplantation
• The subject had cardiovascular clinical symptoms or disease that were not well controlled
• Patients with active hepatitis B or hepatitis C and active pulmonary tuberculosis
• Severe infection (CTCAE\> 2) occurred within 4 weeks prior to initial use of study drug, such as severe pneumonia, bacteremia, infection requiring hospitalization; baseline chest imaging indicated active lung inflammation, symptoms and signs of infection within 2 weeks prior to initial use of study drug or the need for oral or intravenous antibiotics, except for prophylactic antibiotics
• Major surgery (except diagnostic surgery) within 28 days prior to treatment, or is expected to undergo major surgery during the study
• Any other malignancy had been diagnosed within 5 years prior to the first use of study drug, except for nausea tumors with low risk and mortality (5-year survival\> 90%), such as adequately treated basal or squamous cell skin carcinoma or carcinoma of the cervix
• Female patients during pregnancy or lactation and who were refused or unable to use contraception
• At the discretion of the investigator, the subject had other factors that could contribute to his forced termination

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Army Medical Center of PLA — Chongqing

Identifiers

NCT: NCT06354530 · 2023 (315)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗