Esophageal Squamous Cell Carcinoma, Neoadjuvant Therapy
Conditions
Keywords
Camrelizumab, Ivarmacitinib
Brief summary
In the management of locally advanced esophageal squamous cell carcinoma, the outcomes associated with surgical resection, whether conducted alone or supplemented with postoperative adjuvant radiotherapy and chemotherapy, have been suboptimal. Immune checkpoint inhibitors (ICIs) have shown potential in enhancing the immune system's capacity to target and eliminate cancer cells. Evidence suggests that the concurrent administration of JAK inhibitors with ICIs may improve anti-cancer efficacy, increase patient response rates, and prolong progression-free survival compared to ICIs alone. This prospective, exploratory study aims to assess the efficacy of combining camrelizumab, chemotherapy, and Ivarmacitinib in neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma, with the objective of broadening therapeutic options for this malignancy.
Detailed description
In the management of locally advanced esophageal squamous cell carcinoma, the outcomes associated with surgical resection, whether conducted alone or supplemented with postoperative adjuvant radiotherapy and chemotherapy, have been suboptimal. The high risk of local recurrence and distant metastasis, which affect patient prognosis and survival rates. Preoperative immunotherapy holds the potential to activate the patient's immune system to recognize tumor antigens and establish immune memory, thereby enabling the immune system to maintain its surveillance role following surgical tumor resection. Consequently, there is a growing emphasis on the administration of immunotherapy prior to surgery across various solid tumor types. Immune checkpoint inhibitors (ICIs) have shown potential in enhancing the immune system's capacity to target and eliminate cancer cells. However, a substantial subset of patients either responds inadequately or develops resistance to these therapies. To address this challenge, numerous combination treatment strategies have been explored in clinical research. Evidence suggests that the concurrent administration of JAK inhibitors with ICIs may improve anti-cancer efficacy, increase patient response rates, and prolong progression-free survival compared to ICIs alone. Notably, there is a paucity of research regarding the combination of camrelizumab with chemotherapy and Ivarmacitinib as a neoadjuvant therapy. This prospective, exploratory study aims to assess the efficacy of combining camrelizumab, chemotherapy, and Ivarmacitinib in neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma, with the objective of broadening therapeutic options for this malignancy.
Interventions
COMBINATION_PRODUCTCamrelizumab, Chemotherapy and Ivarmacitinib
The treatment regimen includes the administration of Camrelizumab at a dose of 200 mg, Paclitaxel (albumin-bound) at 260 mg/m², and Carboplatin with an area under the curve (AUC) of 5. These medications are administered every 3 weeks for a total of 3 cycles. Additionally, Ivarmacitinib tablets are administered orally at a dosage of 4 mg daily during the first and second cycles, but are omitted during the third cycle, totaling 42 days of administration.
PROCEDUREEsophagectomy
Prior to each surgical procedure, the department engaged in comprehensive discussions to determine and establish the most appropriate course of action. Depending on the tumor location, a minimally invasive Ivor-Lewis (intrathoracic anastomosis) or McKeown (neck anastomosis) esophagectomy, including two-field extensive lymphadenectomies, was performed. The resection length was required to be at least 5 cm from the tumor origin, as determined by pre-chemotherapy endoscopy. These surgeries were conducted by surgeons with extensive experience. Minimally invasive esophagectomy could be performed using the da Vinci surgical robot, thoracoscope, or laparoscope, or through an open approach, as deemed appropriate by the surgeon.
OTHERSample
Blood, Tumour will be Collected from participant. Fate of sample is Destruction after use. 5 ml of peripheral blood was collected the day before each of the immunotherapy sessions and after surgery. Tumour sample will be collected before neoadjuvant therapy and during surgery.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of pathological complete response (PCR) | 1 month after surgery | The proportion of the surgical population with PCR, which was defined no residual invasive tumor cells were found in the pathological examination of resected specimens, including the primary tumor and lymph nodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of major pathological response (MPR) | 1 month after surgery | The proportion of the surgical population with MPR, which was defined in the pathological examination of resected specimens, the proportion of residual tumor cells was less than 10%. |
| Rate of objective response rate (ORR) | before surgery] | The proportion of subjects with imaging PR or CR assessed according to RECIST 1.1 criteria |
| 2-year and 5-year event free survival (EFS) | 2-year and 5-year after enrolled | The proportion of study cases from the time of enrollment to either the occurrence of disease recurrence or death from any cause, whichever occurred first, was analyzed within both 2-year and 5-year intervals. |
| Incidence of Treatment-related Adverse Events | 1 month after surgery | Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0 |
| The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients | 3 month after surgery | By using mass spectrometry (CyTOF), single-cell analysis, and other detecting techniques , we comprehensively characterized the immune landscape in the peripheral blood and tumor sample of ESCC patients before and after anti- PD-1 immunotherapy, aiming to explore the immune subsets correlated with neoadjuvant immunotherapy response. |
Countries
China
Contacts
CONTACTZixiang Ｗu, M.D
STUDY_CHAIRJianan Wang
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Outcome results
None listed