Trial Title:
PPIO-004 Clinical Application of Efficacy Prediction Model Based on Epigenomics Sequencing Technology in Neoadjuvant Immunotherapy for Esophageal Cancer
NCT ID:
NCT05880082
Condition:
Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Esophageal Neoplasms
Esophageal Squamous Cell Carcinoma
Cisplatin
Carboplatin
Tislelizumab
Nedaplatin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Enrolling by invitation
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
The study was a one-arm open study
Intervention:
Intervention type:
Drug
Intervention name:
Tislelizumab
Description:
Tislelizumab 200mg, Q3W, 2-4 cycles Albumin paclitaxel 240 mg/m², adjusted according to
the patient Carboplatin: AUC=5 Q3W, d1 or cisplatin: 20mg/m² iv, D1-3 Q3W or Nedaplatin:
70mg d1 Q3W
Arm group label:
tislelizumab, Q3W with TP regimen
Other name:
Carboplatin
Other name:
cisplatin
Other name:
Nedaplatin
Summary:
The goal of this observational study is to learn about in potential operable esophageal
cancer patients (cT1-2N + M0 and cT3NanyM0) receiving neoadjuvant therapy. The main
questions it aims to answer are: Objective response rate, Major pathological response
rate. Participants will receive two to four cycles of tislelizumab plus albuminpaclitaxel
and platinum-based therapy
Detailed description:
Esophageal cancer is the eighth most common cancer in the world (934,870 new cases) and
the sixth most common cause of cancer death (287,270 new cases). The incidence,
prevalence and histological type of esophageal cancer vary by region. About 75% of cases
occur in Asia, with China accounting for the highest proportion, accounting for about 50%
of the total number of cases and cancer-specific deaths. According to China's National
Bureau of Statistics in 2022, there were 252,500 cases of esophageal cancer and 193,900
deaths in China in 2016, making esophageal cancer the sixth most common cancer and the
fifth leading cause of cancer death in the country. The etiologies of the two most common
histological subtypes (esophageal squamous cell carcinoma [ESCC] and adenocarcinoma) vary
widely. In the West, heavy drinking and smoking and their synergies are major risk
factors for ESCC [3]. However, in low-income countries, such as parts of Asia and
sub-Saharan Africa, the major risk factors for ESCC (which typically accounts for more
than 90% of all esophageal cancer cases) have not been elucidated.
For subjects with locally advanced ESCC, international treatment guidelines recommend
esophagectomy followed by preoperative chemoradiotherapy.
However, in the clinical practice, many subjects with locally advanced ESCC receive
neoadjuvant chemotherapy rather than neoadjuvant chemoradiotherapy, due to safety
concerns regarding the use of radiotherapy in neoadjuvant therapy and difficulties in
cross-clinical collaboration, and may not receive the best benefit from neoadjuvant
therapy. For the preoperative treatment of locally advanced esophageal cancer,
preoperative chemotherapy also has a better survival benefit than surgery alone. In the
Medical Research Council OEO2 study, median survival was 16.8 months in the preoperative
chemotherapy group and 13.3 months in the surgery alone group, with 2-year survival rates
of 43% and 34%, respectively. Long-term follow-up confirmed that preoperative
chemotherapy had a survival benefit, with 5-year survival rates of 23% in the
preoperative chemotherapy group and 17.1% in the surgery alone group. And data on other
immune checkpoint inhibitors suggest that neoadjuvant chemotherapy combined with
immunotherapy improves clinical outcomes.
PD-1 inhibitors have demonstrated significant benefits as second-line and first-line
therapy for ESCC and in combination with chemotherapy for many other solid tumors.
Preclinical studies have shown that the PD-1/PD-L1 axis can be activated early in solid
tumors, and the preoperative induction of immune response may have a lasting protective
effect. Preoperative immunotherapy is likely to be more effective given that the tumor
antigen drops sharply after surgical resection and the removal of intact blood vessels
and lymph nodes that deliver the drug may affect immunotherapy efficacy. Several Phase
1/2 and 2 studies have shown a controllable safety profile and preliminary demonstration
of efficacy when adding PD-1/PD-L1 inhibitors to perioperative treatment in resectable EC
subjects. PD-1 inhibitors have shown significant benefits in both second-line and
first-line treatment. Given the evidence of antitumor activity of immunotherapy in
patients with ESCC and the continuing need to improve survival and reduce recurrence
rates of resectable esophageal cancer, several studies exploring the antitumor activity
of immunotherapy in the treatment of resectable disease have tentatively shown promising
prospects as a neoadjuvant therapy.
tislelizumab, as an innovative PD-1 inhibitor, has shown similar benefits to other PD-1
inhibitors in a variety of tumor types. Bb-a317-205 also showed preliminary antitumor
activity in ESCC subjects, with a confirmed ORR of 46.7%, DCR of 80%, and DOR of 12.8
months. The median OS was 14.31 months. In addition, three pivotal Phase 3 studies in the
ESCC field are underway (studies BGB-A317-302, BGB-A317-306, BGB-A317-311, and
BGB-A317-213).
Therefore, the combination of neoadjuvant chemotherapy with tislelizumab may be a
potential treatment option to improve the benefit of potentially resectable locally
advanced ESCC subjects.
Cancer survival rates are often low, most likely due to advanced stage of diagnosis and
limited access to timely and reasonable treatment. Early and accurate detection of cancer
is important for clinical diagnosis, effective toxicity monitoring, and ultimately
successful treatment of cancer. In the context of the current "precision medicine"
concept, disease assessment should selectively obtain and extract key biological
information from clinical phenotypes, pathological characteristics and molecular
information of diseases, and carry out qualitative, positioning, quantitative and
periodic accurate analysis of these information, laying the foundation for disease
classification, clinical decision-making and prognosis. Based on accurate analysis of
patients' biological information, treatment principles, rules and guidelines based on
empirical evidence, combined with patients' unique physiological, psychological, social
characteristics and personal will, effective treatment methods are wisely selected and
integrated to form the best treatment plan that fits patients' unique characteristics.
In the context of the current "precision medicine" concept, disease assessment should
selectively obtain and extract key biological information from clinical phenotypes,
pathological characteristics and molecular information of diseases, and carry out
qualitative, positioning, quantitative and periodic accurate analysis of these
information, laying the foundation for disease classification, clinical decision-making
and prognosis. At present, several prediction models for evaluating the efficacy and
prognosis of patients have been developed by using public databases at home and abroad.
However, due to the small sample size, less information included in the models and lack
of clinical practice, the reliability is weak.
Therefore, new biomarkers need to be developed to better select patients, and the
development of strong biomarkers and improved patient selection will be key to
combination immunotherapy.
Objective response rate, major pathological response rate, pathological complete response
rate, overall survival, progression-free survival, disease control rate, duration of
response, R0 removal rate, adverse events, and potential predictive biomarkers were
evaluated in patients undergoing surgery after tirelizumab combined with chemotherapy as
neoadjuvant therapy. Explore potential Cancer biomarkers in patients undergoing surgery
after receiving tislelizumab combined with chemotherapy as neoadjuvant therapy
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. ≥18 years old;
2. Pathology (histology) confirmed potentially resectable stage cT1-2N + M0 and stage
cT3NanyM0 ESCC (AJCC 8th edition); 3. Received tirelizumab combined with
chemotherapy before surgery; 4.ECOG score: 0 or 1; 5. R0 radical excision can be
performed; 6. Measurable or evaluable lesions assessed by the investigator according
to RECIST version 1.1; 7. With my consent and signed informed consent, I shall
comply with the planned visit, research treatment, laboratory examination and other
test procedures.
Exclusion Criteria:
1. Patients with other malignant tumors;
2. Prior treatment for ESCC, including chemotherapy, radiotherapy, or prior antibody or
drug therapy against PD-1, anti-PD-L1, anti-PD-L2, or any other specific T-cell
costimulation or checkpoint pathway;
3. They are not eligible to receive platinum-containing double-drug chemotherapy
regimen, chemoradiotherapy or surgery;
4. Patients with a history of fistulas caused by primary tumor infiltration, patients
assessed by the investigator as being at high risk of fistulas or showing signs of
perforation, and severe malnutrition;
5. Poorly controlled pleural effusion, pericardial effusion or ascites requiring
frequent drainage (recurrence within 2 weeks after intervention)
6. Known human immunodeficiency virus (HIV) testing history or known acquired
immunodeficiency syndrome (AIDS);
7. A history of interstitial lung disease, non-infectious pneumonia or poorly
controlled lung disease (including pulmonary fibrosis, acute lung disease, etc.);
8. Any positive test result for hepatitis B virus or hepatitis C virus indicating the
presence of a virus, such as hepatitis B surface antigen (HBsAg, Australian antigen)
positive or hepatitis C antibody (anti-HCV) positive (except HCV-RNA negative);
9. Those who have a history of drug abuse and cannot abstain or have mental disorders;
10. Known history of allogeneic organ transplantation or allohematopoietic stem cell
transplantation;
11. Patients who are participating in other clinical trials or participating in other
clinical trials with less than 4 weeks to end;
12. Pregnant or lactating women;
13. Patients with a BMI < 18.5mg/m2 or a weight loss greater than 10% before screening;
14. Other conditions that the researchers believe will affect the progress of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Army Medical Center of the People's Liberation Army
Address:
City:
Chongqing
Zip:
400042
Country:
China
Start date:
April 13, 2023
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Agency class:
Other
Source:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05880082
