Sintilimab and Anlotinib Combined With Chemotherapy in Neoadjuvant Treatment of Resectable Esophageal Cancer

• ClinicalTrials.gov Identifier: NCT06015035
• Recruitment Status: Completed
• First Posted: August 29, 2023
• Last Update Posted: August 29, 2023
• Sponsor: Tang-Du Hospital
• Information provided by (Responsible Party): Xiaolong Yan, Dr., Tang-Du Hospital

Tracking Information

• First Submitted Date: August 17, 2023
• First Posted Date: August 29, 2023
• Last Update Posted Date: August 29, 2023
• Actual Study Start Date: April 1, 2021
• Actual Primary Completion Date: April 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2023)

Primary Endpoints: pCR [ Time Frame: up to 24 months ]

PCR: This was assessed by examining the postoperative pathological tissue for the absence of tumor cells in the primary tumor and lymph nodes.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sintilimab and Anlotinib Combined With Chemotherapy in Neoadjuvant Treatment of Resectable Esophageal Cancer
• Official Title: A Prospective Single-center, Single-arm, Open-label Study of Sintilimab and Anlotinib Combined With Chemotherapy in Neoadjuvant Treatment of Resectable Esophageal Cancer
• Brief Summary: The study focused on patients with T2-4NxM0 resectable esophageal carcinoma. Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles. Surgical treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) rate and safety.

Detailed Description

The study was conducted from April 2021 to April 2022 at our hospital and was approved by the Ethics Committee of Tangdu Hospital. The inclusion criteria were as follows: patients aged 18-75 years with a histopathologic diagnosis of esophageal cancer staged according to the AJCC eighth edition as T1-4N1-3M0. If patients were staged as T2N0M0, the esophageal lesions had to be ≥5 cm. Before enrollment, all patients underwent various examinations, including cardiac color ultrasound (left ventricular ejection fraction of at least 50%), pulmonary function (forced expiratory volume-1 [FEV1] ≥1.5 L), enhanced chest computed tomography (CT), abdominal color ultrasound, cervical lymph node color ultrasound and other necessary laboratory tests (such as blood routine, liver and kidney function, electrolytes, and cortisol rhythm) to exclude treatment and surgical contraindications and ensure suitability for ICIs treatment.

The exclusion criteria were as follows: Patients unable to tolerate surgery, those with refractory hypertension and proteinuria, those who had previously received other treatments, and those who were not suitable candidates for ICIs (due to conditions such as hepatitis B with viral quantification >2000 IU, systemic lupus erythematosus, and xerosis).

Treatment regimen:

Patients were administered preoperatively with sintilimab (200 mg, Day 1) and anlotinib (10 mg, orally, once daily, 2 weeks on and 1 week off) in combination with chemotherapy (albumin paclitaxel 130 mg/m2, Days 1 and 8 + nedaplatin 80 mg/m2, Day 1) for three cycles of neoadjuvant therapy. Surgical intervention (either Mckeown or Ivor Lewis approach) was performed 4-6 weeks after completing the last treatment cycle of neoadjuvant therapy. After the 4th week after surgery, patients received maintenance therapy with sintilimab (200 mg, Q3W) for 1 year. If any adverse reactions of grade 3 or higher occurred during the treatment, the dose of chemotherapeutic drugs was reduced by 25% until the patient's condition recovered to grade 1 or returned to normal, and the subsequent treatment cycle was continued. In case of grade 3 or higher hypertension or proteinuria, the dose of anlotinib was reduced to 8 mg. It was discontinued if the condition could not recover to grade 1-2 after symptomatic treatment.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Sintilimab and Anlotinib in Combination With Chemotherapy

Intervention

Drug: Sintilimab and anlotinib in combination with chemotherapy

Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles. Surgical treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) rate and safety.

Study Arms

Experimental: anlotinib for anti-angiogenesis and sintilimab and chemotherapy

Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles.

Intervention: Drug: Sintilimab and anlotinib in combination with chemotherapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 27, 2023): 17
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: April 1, 2022
• Actual Primary Completion Date: April 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

• patients aged 18-75 years with a histopathologic diagnosis of esophageal cancer staged according to the AJCC eighth edition as T1-4N1-3M0. If patients were staged as T2N0M0, the esophageal lesions had to be ≥5 cm.
• Before enrollment, all patients underwent various examinations, including cardiac color ultrasound (left ventricular ejection fraction of at least 50%), pulmonary function (forced expiratory volume-1 [FEV1] ≥1.5 L), enhanced chest computed tomography (CT), abdominal color ultrasound, cervical lymph node color ultrasound ▪ other necessary laboratory tests (such as blood routine, liver and kidney function, electrolytes, and cortisol rhythm) to exclude treatment and surgical ontraindications and ensure suitability for ICIs treatment.

Exclusion Criteria:

• Patients unable to tolerate surgery
• those with refractory hypertension and proteinuria
• those who had previously received other treatments
• those who were not suitable candidates for ICIs (due to conditions such as hepatitis B with viral quantification >2000 IU, systemic lupus erythematosus, and xerosis).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT06015035
• Other Study ID Numbers: k202204-02
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: If the clinical study obtains positive results, it will further expand the study

• Current Responsible Party: Xiaolong Yan, Dr., Tang-Du Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Tang-Du Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Tang-Du Hospital
• Verification Date: August 2023