Clinical trial NCT06015035: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sintilimab and Anlotinib in Combination With Chemotherapy
Keywords: esophageal cancer; neoadjuvant; efficiency
Lead sponsor: Tang-Du Hospital
Sponsor class: OTHER
First posted: 2023-08-29
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Primary Endpoints: pCR
timeFrame: up to 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Hongtao Duan
state: Shanxi
city: Xi'an
country: China
facility: Tangdu Hospital, the Air Force Military University
Study officials:
References: