Trial Title:
PD-1 Antibody Combined With mXELIRI Versus mXELIRI in the Second-line Setting for ESCC
NCT ID:
NCT05737563
Condition:
Esophageal Squamous Cell Carcinoma Abdominal Stage 0
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Capecitabine
Irinotecan
Immune Checkpoint Inhibitors
Conditions: Keywords:
PD-1 inhibitor
Capecitabine
Irinotecan
Second-line
Esophageal Squamous Cell Carcinoma
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PD-1 Inhibitors
Description:
Teripulimab 240mg, injection or Carrelizumab 200mg, injection, every 3 weeks.
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
Irinotecan
Description:
Irinotecan: 200mg/m2, injection (For patients who are confirmed to be homozygous for
UGT1A1*6 or UGT1A1*28 or UGT1A1*6 and UGT1A1*28 at the same time, the starting dose of
CPT-11 is 150 mg/m2).
Arm group label:
Control
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
Capecitabine tablets
Description:
Capecitabine: 1600 mg/m2/d, oral, 2 weeks on and 1 week off.
Arm group label:
Control
Arm group label:
Experimental
Summary:
This trial is a prospective, multicenter, randomized controlled trial. The sample size
was 380. Patients with advanced or metastatic esophageal squamous cell carcinoma will be
randomized to receive PD1 antibody combined with mXELIRI or mXELIRI regimens in a 1:1
ratio. The stratification factors include PS status (0 vs 1), PFS of first-line treatment
(PFS < 3 months versus PFS ≥3 months) . Six cycles of chemotherapy are planned every 3
weeks, for a total of 18 weeks, after which the investigator can decide whether to
provide capecitabine with or without PD1 antibody maintenance therapy. Efficacy
assessments were performed every 6 weeks before disease progression during treatment.
Survival status was followed every 3 months after disease progression.
Detailed description:
Esophageal cancer is the seventh most common cancer and the sixth most common cause of
cancer related death worldwide. Globally, there were 604,000 new cases of esophageal
cancer and 544,000 deaths in 2020. China is in the high incidence area of esophageal
cancer, with 253,000 new cases of esophageal cancer and 194,000 deaths in 2016.
Esophageal cancer has become a malignant disease that seriously endangers the health and
social development.
Squamous cell carcinoma and adenocarcinoma are common pathological types of esophageal
cancer. The main risk factors for esophageal squamous cell carcinoma are smoking and
alcohol consumption. Esophageal squamous cell carcinoma is the most important
pathological type of esophageal cancer in China, accounting for more than 90% of
esophageal cancer.
The prognosis of esophageal cancer is very poor, most patients are in the middle and
advanced stages at the time of diagnosis. The natural course of the disease is only 6-8
months, and the 5-year survival rate is less than 20%. In addition, 90% of patients
undergoing surgery may have recurrent metastasis, and even those with very early staging
(T1) still have the risk of relapse or metastasis within 5 years. Therefore, in recent
years, scholars from various countries have continued to explore effective treatment
methods in order to improve the quality of life and prolong the survival of esophageal
cancer patients.
Palliative chemotherapy is the mainstay of treatment for advanced metastatic esophageal
cancer including paclitaxel, platinum, fluorouracil, or irinotecan. Multiple phase III
clinical studies have shown that PD-1 antibodies in addition to PF (fluorouracil plus
cisplatin) or TP (paclitaxel plus cisplatin) regimens can improve the effective rate and
prolong PFS and OS. Therefore, PD-1 antibody combined with chemotherapy has become the
new standard first-line treatment for patients with advanced esophageal cancer.
Prior to the advent of PD-1 antibodies, the second-line regimen for advanced esophageal
cancer was to select drugs that were not used in first-line chemotherapy, such as taxans
or irinotecans. Keynote181, Attraction-03, and ESCORT studies have suggested that PD-1
antibody monotherapy is superior to standard chemotherapy in the second-line treatment of
advanced esophageal cancer. In ESCORT studies, PD-1 antibodies and conventional
chemotherapy (docetaxel or irinotecan) were 20.2 percent and 6.4 percent effective,
median PFS at 1.9 months, and median OS at 8.3 months and 6.2 months, respectively. Based
on the above research results, China's Food and Drug Administration has approved PD-1
antibody for the second-line treatment of advanced esophageal cancer.
Therefore, we intend to design a prospective, multicenter, randomized controlled clinical
study based on the characteristics of esophageal cancer in China, explore the efficacy
and safety of PD-1 antibody combined with mXELIRI compared with mXELIRI in the
second-line treatment of metastatic esophageal squamous cell carcinoma. We will further
analyze the significance of cross-line use of PD-1 antibody and analyze the possible
benefit population.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntarily participate and sign the informed consent form
2. Age≥ 18 years old, gender is not limited
3. Estimated survival time≥ 3 months
4. Physical status ECOG status score of 0 or 1
5. metastatic esophageal squamous cell carcinoma, including patients with postoperative
recurrence and metastasis that cannot be operated or are not suitable for radical
radiotherapy, first-line chemotherapy combined with PD-1 antibody therapy is
unsuccessful or intolerable (first-line chemotherapy does not use fluorouracils and
irinotecan)
6. If metastatic esophageal cancer has serious clinical symptoms due to lesions,
palliative radiotherapy is required first, and radiotherapy is required to be
completed for more than 4 weeks (radiotherapy lesions include but are not limited to
primary lesions, bones, and lymph nodes)
7. Bone marrow hematopoietic function: hemoglobin ≥ 9.0g/dL, white blood cell ≥
4.0×109/L, neutrophil ≥ 1.5×109/L, platelet ≥ 90×109/L
8. Liver and kidney function: total bilirubin ≤ 1.5 × ULN, creatinine ≤ 1.0 × ULN,
AST/ALT ≤ 2.5 ULN, ALP 5.0 ULN, creatinine clearance ≥ 60mL/min, subjects with liver
metastases: AST/ALT ≤5.0 ULN
9. Female subject must have taken reliable contraceptive measures of childbearing
potential should have a negative urine or serum pregnancy within 7 days prior to
receiving the first dose of study medication. and be willing to use an appropriate
method of contraception during the trial and 8 weeks after the last administration
of the test drug. Male subject should agree to use appropriate contraceptive methods
or to have been surgically sterilized during the trial and 8 weeks after the last
administration of the test drug
10. Those who have good compliance and can follow up according to the requirements of
the plan.
Exclusion Criteria:
1. previous useing of fluorouracil or irinotecan for metastatic disease;
2. received radiotherapy within 4 weeks prior to enrollment;
3. patients with symptomatic brain metastases;
4. uncontrolled pleural effusion, pericardial effusion, or ascites that requires
repeated drainage (once a month or more frequently); Multi-segment vertebral bone
metastasis, easy to cause fracture, risk of paraplegia bone metastasis patients.
Except for patients who are assessed by a specialist to be stable and do not need to
be treated for the time being;
5. Patients who are known to have complete endoscopic obstruction and require
interventional treatment or surgery to relieve obstruction and who have undergone
tracheal or esophageal stenting;
6. Can not take oral medication;
7. BMI less than 17.5kg/m2, weight loss of >10% within about 2 months before the first
administration of study treatment (need to consider a large number of pleural
ascites changes) or other indicators show severe malnutrition;
8. Those who are allergic to the drugs used in this program or their components;
9. patients receiving chronic or multi-dose corticosteroid therapy (inhaled steroids or
short-term oral cortisol as clinically indicated are allowed);
10. History of autoimmune diseases, including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, antiphospholipid syndrome-related vascular thrombosis,
Wegener's granulomatous disease, Sjogren's syndrome, Guillain-Barré syndrome,
multiple sclerosis, vasculitis, glomerulonephritis, etc. Patients who are
hypothyroid but receiving a stable dose of thyroid hormone replacement therapy may
be enrolled in this study; Patients with type 1 diabetes who are treated with a
stable dose of insulin dosing regimen and whose blood glucose is controlled may be
enrolled in this study;
11. Patients with positive human immunodeficiency virus (HIV) test results
12. Patients with active pulmonary tuberculosis (clinical diagnosis includes clinical
history, physical examination and imaging findings, and TB examination according to
local medical practice);
13. received oral or intravenous antibiotics within 2 weeks prior to randomization;
Patients receiving prophylactic antibiotic therapy (eg, to prevent urinary tract
infection or to prevent exacerbation of chronic obstructive pulmonary disease) may
be enrolled.
14. Important cardiovascular diseases, such as heart disease (grade II or higher) as
defined by the New York College of Cardiology, myocardial infarction within 3 months
prior to randomization, unstable arrhythmia, unstable angina, cerebrovascular
accident or transient ischemic attack; 50% of patients with known coronary artery
disease, congestive heart failure that does not meet the above criteria, or left
ventricular ejection fraction < must be treated with a stable regimen deemed best by
the attending physician, and if necessary, a cardiologist;
15. Chronic hepatitis B carriers with untreated chronic hepatitis B or HBV DNA > 1000
IU/mL at the time of screening. Note: Inactive hepatitis B surface antigen (HBsAg)
carriers, treated and stable hepatitis B patients (HBV DNA < 1000 IU/mL) can be
enrolled;
16. Had major surgery (other than diagnostic surgery) within 28 days prior to
randomization, or was expected to undergo major surgery during the study period;
17. Previous allogeneic bone marrow transplantation or solid organ transplantation;
18. Patients with serious complications, such as active gastrointestinal bleeding,
perforation, jaundice, gastrointestinal obstruction, and active infection; Including
but not limited to infection complications requiring hospitalization, bacteremia,
severe pneumonia, etc.; history of idiopathic pulmonary fibrosis, organising
pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonia, idiopathic
pneumonia, interstitial pneumonia, or evidence of active pneumonia on chest CT scan
screening;
19. Neurological or psychiatric abnormalities affecting cognitive ability;
20. pregnant or lactating women;
21. Those who have participated in other clinical studies in the past 30 days;
22. Previous PD1 antibody therapy with grade 3 immune-related adverse reactions greater
than or equal to 3
23. Patients with other primary malignant tumors other than esophageal cancer (except
cured skin basal cell carcinoma and cervical carcinoma in situ);
24. Any other disease, metabolic disorder, abnormal result of physical examination or
laboratory test that has reason to suspect may lead to contraindications to the use
of the investigational drug, or affect the reliability of the results of the study,
or put the patient at high risk of treatment complications.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Miao-Zhen Qiu, MD, PhD
Phone:
+862087343351
Email:
qiumzh@sysucc.org.cn
Investigator:
Last name:
Rui-Hua Xu
Email:
Principal Investigator
Investigator:
Last name:
Miao-Zhen Qiu
Email:
Sub-Investigator
Investigator:
Last name:
Feng Wang
Email:
Sub-Investigator
Start date:
February 17, 2023
Completion date:
February 17, 2026
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
Shanghai Junshi Bioscience Co., Ltd.
Agency class:
Other
Collaborator:
Agency:
Jiangsu HengRui Medicine Co., Ltd.
Agency class:
Industry
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05737563
