Clinical trial NCT06576973: Adbelimumab Combined With Chemotherapy and Apatinib in Patients With Resectable Esophageal Squamous Cell Carcinoma
Official title: A Prospective, Single-arm, Single-center, Exploratory Study of the Safety and Efficacy of Adbelimumab Combined With Chemotherapy and Apatinib in Patients With Resectable Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Neoadjuvant Treatment
Keywords: Adbelimumab
Chemotherapy
Apatinib
Esophageal Squamous Cell Carcinoma
Neoadjuvant Treatment
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2024-08-29
Enrollment: 35
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: Esophageal cancer is a prevalent digestive tract tumor, with around 400,000 new cases and 300,000 deaths globally each year. In the past few decades, surgery, radiotherapy, chemotherapy and other treatments were continuously improved, however, the mortality of esophageal squamous cell carcinoma (ESCC) patients was not significantly decreased. For patients with locally advanced esophageal cancer, direct surgery is not effective. It is difficult to achieve radical resection by surgery merely, and even if many patients receive surgery, they may eventually have tumor recurrence and poor survival rate.

Therefore, it is necessary to explore effective perioperative neoadjuvant treatment to reduce the risk of postoperative recurrence and improve the postoperative survival rate of patients. According to the reports, the expression of PD-L1 in esophageal cancer was about 41.4%. Therefore, PD-1/ PD-L1 immunocheckpoint inhibitor may become a new method for the treatment of ESCC. Preliminary clinical results showed that immunotherapy combined with chemoradiotherapy provided a synergies antitumor effect.

The results of the Phase 1b trial evaluating adbelimumab monotherapy as a neoadjuvant treatment for locally advanced resectable ESCC demonstrated that patients receiving two cycles of neoadjuvant sequential surgery exhibited favorable safety profiles, with no adverse reactions of grade 3 or higher. The trial reported a major pathological response (MPR) rate of 24%, a pathological complete response (pCR) rate of 8%, a 2-year overall survival (OS) rate of 92%, and a 2-year recurrence-free survival (RFS) rate of 100%. The effectiveness of combining adbelizumab with chemotherapy and targeted therapy for locally advanced esophageal cancer is uncertain.

This study aims to assess the efficacy and safety of using adbelizumab with chemotherapy and apatinib as neoadjuvant therapy for resectable ESCC.


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent.
2. Patients age 18 to 75 years old.
3. Primary resectable, histologically confirmed esophageal squamous cell cancer.
4. Esophageal squamous cell carcinoma the clinical stage was II-IVA (according to AJCC TNM stage, 8th edition).
5. ECOG PS 0-1.
6. No distant metastasis, the diseases could be resectable assessed by thoracic oncologist.

Exclusion Criteria:

1. With significant cardiovascular disease.
2. Current treatment with anti-viral therapy or HBV.
3. Female patients who are pregnant or lactating.
4. History of malignancy within 5 years prior to screening.
5. Active or history of autoimmune disease or immune deficiency.
6. Signs of distant metastases.

Primary outcomes:
measure: Pathological Complete Response (PCR)
timeFrame: 1 month after surgery
Secondary outcomes:
measure: Major Pathological Response (MPR)
timeFrame: 1 month after surgery
measure: Objective Response Rate (ORR)
timeFrame: before surgery
measure: The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients
timeFrame: 3 months after surgery
measure: 2-year and 5-year overall survival
timeFrame: 2-year and 5-year after enrolled
measure: Incidence of Treatment-related Adverse Events
timeFrame: 1 month after surgery
measure: R0 resection rate
timeFrame: 1 month after surgery
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: 2nd Affiliated Hospital, School of Medicine, Zhejiang University
Study officials:
affiliation: 2nd Affiliated Hospital, School of Medicine, Zhejiang University
name: Wang
role: STUDY_CHAIR
References: