Trial Title:
Neoadjuvant Therapy for Stage II-IVA Resectable Esophageal Squamous Cell
NCT ID:
NCT06006650
Condition:
Neoadjuvent
PD-1 Inhibitor
Chemotherapy
Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Paclitaxel
Pembrolizumab
Fluorouracil
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab, Albumin Paclitaxel, 5-fluorouracil, Cisplatin
Description:
Pembrolizumab, Albumin Paclitaxel, 5-fluorouracil, Cisplatin
Arm group label:
5-fluorouracil and Cisplatin
Arm group label:
Pembrolizumab Plus 5-fluorouracil and Cisplatin
Arm group label:
Pembrolizumab Plus Albumin Paclitaxel and Cisplatin
Summary:
The aim of this study was to investigate the efficacy and safety of pembrolizumab
combined with albumin paclitaxel and cisplatin versus albumin paclitaxel and cisplatin or
5-fluorouracil and cisplatin in neoadjuvant therapy for stage II-IVa resectable
esophageal squamous cell carcinoma. The study plans to enroll 114 eligible patients who
will be randomly assigned in a 1:1:1 ratio to receive 3 cycles of neoadjuvant
immunochemotherapy (pembrolizumab plus albumin paclitaxel and cisplatin;Pembrolizumab
plus 5-fluorouracil and cisplatin) or chemotherapy alone (5-fluorouracil and cisplatin),
followed by surgery 3 weeks later, followed by 16 cycles of adjuvant immunotherapy
(pembrolizumab).Patients were followed up for efficacy and safety during treatment.Tumor
evaluation will be performed at screening, after neoadjuvant therapy, before surgery, and
after adjuvant therapy until objective disease progression is confirmed.
Detailed description:
The aim of this study was to investigate the efficacy and safety of pembrolizumab
combined with albumin paclitaxel and cisplatin versus albumin paclitaxel and cisplatin or
5-fluorouracil and cisplatin in neoadjuvant therapy for stage II-IVa resectable
esophageal squamous cell carcinoma. The study plans to enroll 114 eligible patients who
will be randomly assigned in a 1:1:1 ratio to receive 3 cycles of neoadjuvant
immunochemotherapy (pembrolizumab plus albumin paclitaxel and cisplatin;Pembrolizumab
plus 5-fluorouracil and cisplatin) or chemotherapy alone (5-fluorouracil and cisplatin),
followed by surgery 3 weeks later, followed by 16 cycles of adjuvant immunotherapy
(pembrolizumab).Patients were followed up for efficacy and safety during treatment.Tumor
evaluation will be performed at screening, after neoadjuvant therapy, before surgery, and
after adjuvant therapy until objective disease progression is confirmed.
Study Endpoints Primary Endpoints PCR: This was assessed by examining the postoperative
pathological tissue for the absence of tumor cells in the primary tumor and lymph nodes.
Safety: Adverse reactions during neoadjuvant therapy were recorded following CTCAE
version 5.0 guidelines. Perioperative complications were assessed using the Clavien-Dindo
classification. Grade I complications included any deviation from the normal
postoperative recovery process without requiring medical, surgical, endoscopic, or
radiological intervention. Acceptable medical management included antiemetics,
antipyretics, analgesics, diuretics, electrolytes, and physical therapy. Bedside open
incisional infections were included under this category. Grade II complications were
those that required medications beyond those used for treating Grade 1 complications,
including blood transfusions and total parenteral nutrition. Grade III complications were
those that required surgical, endoscopic, or radiological intervention. Grade IV
complications were those considered life-threatening and requiring mid-term care or
admission to an intensive care unit (including central nervous system complications, such
as cerebral hemorrhage, ischemic stroke, and subarachnoid hemorrhage, and excluding
transient ischemic attacks). Grade V complications included patient deaths.
Secondary Endpoints
1) Major pathological response (MPR) refers to the proportion of residual tumor cells
in the primary tumor and lymph nodes in the postoperative pathological tissue being
<10%, or the primary tumor completely disappearing, and the number of positive lymph
nodes being ≤1. 2) R0 resection rate: R0 resection was defined as achieving negative
upper and lower resection margins. 3) RECIST Criteria Assessment: Complete response
(CR): complete response of target lesions; PR: >30% regression of target lesions;
Non-CR/Non-PD: target lesions did not completely disappear and did not increase by
>20%, or other new lesions appeared in the body; Stable disease (SD): target lesions
were reduced or increased by <20%; Progressive disease (PD): target lesions had
increased by >20%.
Statistical Methods The sample size was determined using Simon's two-stage design. With a
minimum expected pCR of 20% and an expected pCR of 40%, a Type I error (α) of 0.05, and a
Type II error of 80%, a sample size of 34 was calculated. In the first stage, 17 patients
were enrolled. The study was carefully monitored to limit the number of pCR cases to
three or below, and any increase in the risk of surgery and mortality due to the
treatment regimen would have led to its discontinuation. All continuous variables were
presented as frequencies. Statistical significance was set at P <0.05.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1.Pathological diagnosis: esophageal squamous cell carcinoma. 2.18-75 years old;
3.Clinical stage II-IVa; 4.no prior antitumor therapy, such as immunotherapy or
chemoradiotherapy; 5.ECOG PS score 0-1. 6.Organs function well:Hemoglobin ≥100g/L, white
blood cell count ≥4*10^9/L or neutrophil count ≥2.5*10^9/L, platelet count ≥100*10^9/L,
serum total bilirubin level ≤1.5 times the upper limit of normal, aspartate
aminotransferase (AST) ≤2.5 times the upper limit of normal,Alanine aminotransferase
(ALT) ≤2.5 times the upper limit of normal, serum creatinine level below the upper limit
of normal or creatinine clearance rate ≥60ml/min, urea nitrogen ≤200mg/L, urinary protein
<+, if urinary protein +, 24-hour total protein must be <500mg, blood glucose:In patients
with normal-range and/or diabetes under treatment but stable glycemic control, pulmonary
function: baseline FEV1 of at least 2L;If the baseline FEV1 was <2L, the predicted FEV1
after surgery was >800ml, and the cardiac function was: no myocardial infarction within 1
year;Unstable angina pectoris;Asymptomatic severe arrhythmias;The centerless function is
incomplete; 7.Non-surgically sterilized women, or women of reproductive age, need to use
a medically approved contraceptive method (such as an intrauterine device, birth control
pill, or condom) during and for 3 months after the end of the study treatment
period.Women of childbearing age who were not surgically sterilized had to have a
negative serum or urine HCG test within 72 hours before study enrollment.And must be
non-lactation period;For male patients with partners of women of childbearing age,
effective methods of contraception should be used during the trial period and within 3
months after the last dose of treatment; 8.Sign an informed consent form.
Exclusion Criteria:
1. Pathological findings suggest compound squamous cell carcinoma, including squamous
adenocarcinoma, squamous cell carcinoma, carcinosarcoma, sarcomatoid carcinoma, etc.
2. History of subtotal gastrectomy;
3. accompanied by a second primary cancer;
4. Tumor metabolic imaging prior to treatment suggested distant metastasis.
5. people who have previously received chemoradiotherapy;
6. preesophageal perforation signs
7. pregnant women of reproductive age;
8. Any active autoimmune disease or a history of autoimmune disease (such as autoimmune
hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis,
myocarditis, nephritis, hyperthyroidism, hypothyroidism, etc.);
9. People with the following active infectious diseases, including active tuberculosis,
hepatitis, and known human immunodeficiency virus (HIV) infection;
10. Someone who has a known or concomitant hemorrhagic disease or other uncontrollable
disease that cannot be treated surgically;
11. Physical examination or clinical trial findings that researchers believe could
interfere with the outcome or put the patient at increased risk of treatment
complications;
12. A previous history of interstitial lung disease, drug-induced interstitial disease,
radiation pneumonitis requiring hormone therapy, or any clinically documented active
interstitial lung disease, and the presence of idiopathic pulmonary fibrosis on CT
scan at baseline;Uncontrolled massive pleural or pericardial effusion;
13. unstable systemic diseases (active infection, moderately severe chronic obstructive
pulmonary disease (copd), poorly controlled hypertension, unstable angina and
congestive heart failure, 6 months occurrence of myocardial infarction, drug control
severe mental disorders, liver, kidney or other metabolic disease, nerve mental
disease such as Alzheimer 's disease);
14. Gastrointestinal dysfunction, malabsorption syndrome, active gastrointestinal
ulcers;
15. Previously treated with anti-PD-1 or anti-PD-L1 antibodies;
16. Receiving any investigational drug within 4 weeks before the first use of the
investigational drug;
17. Enroll in another clinical study at the same time, unless it's an observational
(non-intervention) clinical study or an intervention clinical study follow-up;
18. Subjects who require systematic treatment with corticosteroids (equivalent dose of
prednisone > 10 mg per day) or other immunosuppressive agents within 2 weeks prior
to the first use of the study drug, except for the use of corticosteroids for local
esophageal inflammation and prevention of allergy, nausea, and vomiting.Other
special circumstances, need to communicate with the sponsor.In the absence of active
autoimmune disease, inhaled or topical steroids and adrenocorticosteroid replacement
at doses > 10mg/ day in response to prednisone are permitted;
19. People who have been vaccinated with anti-tumor vaccine or who have been vaccinated
with live vaccine within 4 weeks prior to the first administration of the study
drug;
20. Major surgery or severe trauma within 4 weeks before the first use of the study
drug;
21. Congenital or acquired immunodeficiency disease or a history of organ
transplantation;A history of allergies to monoclonal antibodies, albumin paclitaxel,
5-fluorouracil, cisplatin, and other platinum-based drugs
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Tangdu Hospital of the Fourth Millitary Medical University
Address:
City:
Xi'an
Zip:
710038
Country:
China
Status:
Recruiting
Contact:
Last name:
Xiaolong Yan, MD
Phone:
+862984717558
Email:
yanxiaolong@fmmu.edu.cn
Investigator:
Last name:
Xiaolong Yan, MD
Email:
Sub-Investigator
Investigator:
Last name:
Tao Jiang, MD
Email:
Principal Investigator
Facility:
Name:
Hongtao Duan
Address:
City:
Xi'an
Zip:
710038
Country:
China
Status:
Recruiting
Contact:
Last name:
Hongtao Duan, MD
Email:
646014852@qq.com
Investigator:
Last name:
Xiaolong Yan, MD
Email:
Sub-Investigator
Investigator:
Last name:
Tao Jiang, MD
Email:
Principal Investigator
Facility:
Name:
Tangdu Hospital, the Air Force Military University
Address:
City:
Xi'an
Zip:
710038
Country:
China
Status:
Recruiting
Contact:
Last name:
Xiaolong Yan, Dr.
Phone:
029-847171569
Email:
yanxiaolong@fmmu.edu.cn
Start date:
August 1, 2022
Completion date:
December 31, 2031
Lead sponsor:
Agency:
Tang-Du Hospital
Agency class:
Other
Source:
Tang-Du Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06006650
