Trial Title:
Safety and Efficacy of Pembrolizumab in Combination With FLOT About Gastroesophageal Junction Cancer:
NCT ID:
NCT06411171
Condition:
Gastroesophageal Junction Cancer
Conditions: Official terms:
Leucovorin
Pembrolizumab
Docetaxel
Oxaliplatin
Fluorouracil
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Triple (Participant, Care Provider, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab plus chemotherapy (FLOT)
Description:
The experimental group was treated with pembrolizumab combined with FLOT, and the control
group was treated with FLOT chemotherapy alone
Arm group label:
Pembrolizumab plus chemotherapy (FLOT)
Arm group label:
chemotherapy (FLOT)
Other name:
docetaxel, oxaliplatin, fluorouracil, and leucovorin (the FLOT regimen)
Summary:
At present, surgery is still the main treatment for gastroesophageal junction cancer. At
the same time, multimodal comprehensive treatment such as chemotherapy and molecular
targeted therapy can effectively alleviate pathological progression, facilitate R0
resection and improve the overall survival of patients.Pembrolizumab, as a PD-1
inhibitor, has been shown to have antitumor activity and a manageable safety profile in
gastroesophageal junction cancer.Pembrolizumab combined with chemotherapy has become a
research hotspot. However, to date, there is no clinical study related to
gastroesophageal junction cancer. In this study, Pembrolizumab combined with FLOT was
used as the first-line treatment for gastroesophageal junction cancer, aiming to explore
the experience chemotherapy mode for gastroesophageal junction cancer.
Detailed description:
Gastric cancer, including gastroesophageal junction cancer, is the fifth most common
cancer and the third leading cause of death in the world. Among them, although the
incidence of distal gastric adenocarcinoma is decreasing, the incidence of
gastroesophageal junction cancer is increasing. At present, surgery is still the main
treatment for gastroesophageal junction cancer. At the same time, multi-mode
comprehensive treatment such as chemotherapy and molecular targeted therapy can
effectively alleviate pathological progression, facilitate R0 resection and improve the
overall survival of patients. A large number of previous clinical trials on the
combination of first-line chemotherapy and molecular targeted drugs in the treatment of
gastric and gastroesophageal junction cancer have shown that only trastuzumab can improve
the overall survival rate of Her-2 positive patients. In addition, despite various
clinical chemotherapy regimens, the median survival time of gastric cancer and
gastroesophageal junction cancer is not high. Therefore, the treatment mode of
gastroesophageal junction cancer, especially for Her-2 negative patients, needs to be
explored and improved.
In recent years, immune checkpoint inhibitors represented by programmed death receptor 1
(PD-1)/programmed death receptor ligand 1 (PD-L1) inhibitors have been applied to the
treatment of a variety of solid tumors such as melanoma, non-small cell lung cancer,
renal cell carcinoma, head and neck cancer, and urothelial cancer. It has become another
important treatment strategy after surgery, chemotherapy, radiotherapy and targeted
therapy. Studies have shown that PD-L1 is highly expressed in tumor cells and immune
cells in gastric cancer and gastroesophageal junction cancer and plays a key role in
tumor immune escape, therefore, the PD-1/ PD-L1 pathway will become an important target
for effective intervention in gastroesophageal junction cancer. As a PD-1 inhibitor,
Pembrolizumab has been shown to have anti-tumor activity and manageable safety in
gastroesophageal junction cancer, and was approved by the US FDA in September 2017 for
advanced PD-L1-positive gastric or gastroesophageal junction cancer . The phase Ⅱ
KEYNOTE-059 trial used Pembrolizumab as a single agent in the third-line treatment of
advanced gastric or gastroesophageal junction cancer, and the results showed that it had
controllable safety in patients with PD-L1 positive, with obvious advantages in objective
response rate (ORR) and median duration of response (DOR) [12]. Chemotherapy enhances
tumor immune responses by enhancing tumor cell immunogenicity and sensitivity to immune
killing, and the combination of chemotherapy and immune checkpoint inhibitors has been
shown to improve overall survival in several cancer types. Therefore, PD-1/ PD-L1
immunosuppressant combined with chemotherapy has become a hot spot in the research of
advanced gastric cancer or gastroesophageal junction cancer . The phase 3 KEYNOTE-062
trial compared Pembrolizumab plus chemotherapy (cisplatin plus 5-FU or capecitabine) with
chemotherapy alone or Pembrolizumab alone in the first-line treatment of advanced gastric
or gastroesophageal junction cancer. However, compared with chemotherapy alone,
Pembrolizumab combined with chemotherapy could not significantly prolong the overall
survival of patients, and the overall effect was not better than chemotherapy alone . In
contrast, the phase III KEYNOTE-590 study, designed to compare the efficacy and safety of
Pembrolizumab plus chemotherapy (cisplatin plus fluorouracil) versus chemotherapy alone
as first-line treatment for advanced esophageal and Siwert type I gastroesophageal
junction cancer, showed that Pembrolizumab combined with chemotherapy was significantly
superior to chemotherapy alone . Neither the KEYNOTE-062 trial nor the KEYNOTE-590 trial
analyzed a separate population of patients with gastroesophageal junction cancer, and
there are some differences in response to drugs by tissue type. Therefore, The efficacy
of Pembrolizumab plus chemotherapy in the only patient population with gastroesophageal
junction cancer warrants further investigation.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1) aged from 18 to 75 years old, including 18 and 80 years old;
2) histologically or cytologically confirmed locally advanced unresectable or
metastatic gastric or GEJ adenocarcinoma;
3) ECOG PS score 0 or 1;
4) Known PD-L1 expression (assessed centrally using PD-L1 HC22C3)
5) no previous treatment
6) HER2-negative status
7) normal hematological parameters: white blood cell count ≥4×109/L; Absolute
neutrophil count ≥1.5×109/L; Platelet count ≥100×109/L; Blood red protein g/L;
8) basically normal renal function: serum creatinine ≤1.5×ULN or creatinine
clearance (CrCl)> 60 mL/min(using Cockcroft-Gault formula):
Female CrCl=(140-age)× weight (kg)× 0.85 / (72×Scr mg/dl)
Male CrCl=(140-age)× weight (kg)× 1.00 / (72×Scr mg/dl)
Liver function was basically normal: serum total bilirubin ≤1.5×ULN; Aspartate
aminotransferase (AST) ≤2.5×ULN; Alanine aminotransferase (ALT) ≤2.5×ULN.
Female patients must have a negative urine pregnancy test before the start of the study
(not applicable to patients with bilateral oophorectomy and/or hysterectomy or
postmenopausal patients)
9) Provide written informed consent. Written informed consent was obtained.
Exclusion Criteria:
-
1) receiving anti-tumor therapy before enrollment, including but not limited to
PD-1 inhibitors, CTLA-4 antibodies, EGFR monoclonal antibodies, EGFR-Tkis, and
anti-angiogenic drugs;
2) A history of autoimmune disease, 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 granulomatosis, Sjogren's
syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or
glomerulonephritis. (Note: Patients with vitiligo, type I diabetes, or residual
hypothyroidism due to autoimmune conditions (e.g., after Hashimoto's syndrome)
requiring only hormone-replacement therapy, psoriasis requiring no systemic
therapy, or if recurrence was not expected in the absence of an external
trigger were allowed.) ;
3) participated in other interventional clinical trials within 30 days before
screening;
4) Patients with a history of other malignant tumors (except cured basal cell
carcinoma)
5) with severe uncontrolled comorbidities (e.g., heart failure, diabetes mellitus,
hypertension, liver failure, renal failure, thyroid disease, mental illness,
etc.);
6) known HIV infection or active viral hepatitis or tuberculosis;
7) have a major surgical procedure or planned surgery within 30 days before the
first dose of the trial drug;
8) patients who are allergic to the drugs used in this regimen or their
components;
9) pregnant (confirmed by blood or urine HCG testing) or lactating women, or
childbearing age subjects unwilling or unable to use effective contraception
(for both male and female subjects) until at least 6 months after the last
trial treatment;
10) The investigator considers that it is not appropriate to participate in the
study;
11) unwilling to participate in the study or unable to sign an informed consent
form
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
June 1, 2024
Completion date:
September 1, 2028
Lead sponsor:
Agency:
xiaohua li
Agency class:
Other
Source:
Xijing Hospital of Digestive Diseases
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06411171
