Clinical trial NCT05044728: Exploration of Immunodynamic Monitoring in the Population Evaluation of Neoadjuvant Chemotherapy Immunotherapy in Patients With Solid Tumors of the Chest.
Official title: The Exploration of Immunodynamic Monitoring in the Population Evaluation of Neoadjuvant Chemotherapy Immunotherapy in Patients With Solid Tumor of the Chest.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Esophageal Squamous Cell Carcinoma
Keywords: Anti-PD-1
NSCLC
ESCC
Neoadjuvant
Immune microenvironment
Lead sponsor: Sichuan Cancer Hospital and Research Institute
Sponsor class: OTHER
First posted: 2021-09-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study is a prospective, single-arm, open cohort study (randomly stratified within the group).
Primary purpose: TREATMENT

Brief summary: Chest malignant solid tumor (mainly lung and esophageal cancer) is a common malignant tumor that seriously threatens the health of residents in China. Its morbidity and mortality rank first, sixth, first, and fourth among all malignant tumors respectively. The treatment effect is not satisfactory, and the overall 5-year survival rate after surgery alone is about 20%-35%. Recent studies have shown that neoadjuvant therapy combined with surgery in the treatment of locally advanced esophageal cancer and lung cancer can significantly improve the efficacy compared with surgery alone. The results of multiple international and multi-center neoadjuvant immunotherapy showed that this new model of combined immunoadjuvant immunotherapy brought a breakthrough point for the treatment of malignant solid tumors of the chest. However, its safety and target benefit groups are still the biggest problems, and there is a large room for improvement. To develop the optimal treatment strategy, it is necessary to further clarify the immunomodulatory mechanisms of neoadjuvant CTIO, explore and develop new evaluation methods and prognostic biomarkers for the selection of targeted benefit patients, and the evaluation of efficacy. This is a key scientific issue in the current neoadjuvant CTIO treatment mode for thoracic malignant solid tumors, mainly lung and esophageal squamous cell carcinoma, which urgently needs to solve its safety and select the benefit population.

Detailed description: As a major participant in cellular immunity, CD8-positive T cells are considered to be the main anti-tumor immune effector cells. In addition to producing specific immune responses to viruses and other infections, their functional subsets are closely related to the occurrence and development of major human diseases. Therefore, we have reason to believe that the combination of dynamic monitoring of host immune background and traditional clinical evaluation can effectively clarify the immune background of patients with lung cancer and esophageal squamous cell carcinoma, and provide new ideas and methods for the selection of appropriate immunotherapy regimen and prognosis evaluation. However, the research in this field is still in its infancy.

Eligibility criteria: Inclusion Criteria:

* Patients with locally advanced non-small cell lung cancer (stage II or III) and thoracic esophageal squamous cell carcinoma (CT2N1-2M0, CT3-4AN0-2M0).
* Preoperative biopsy pathology confirmed squamous cell carcinoma or adenocarcinoma with negative driver gene.
* Without any anti-tumor therapy.
* Endoscopic examination indicated that the midpoint of the tumor was located in the middle and lower esophageal thoracic segments.
* Preoperative staging is II or III.
* Ages 18 to 72 years.
* Cardiopulmonary, liver and kidney function tests can tolerate surgery.
* ECOG PS 0-1.
* Signed the informed consent to participate in the study plan before enrollment.

Exclusion Criteria:

* Preoperative endoscopic biopsy pathology confirmed small cell carcinoma.
* Has undergone other anti-tumor therapy.
* Endoscopic examination indicated that the midpoint of the tumor was located in the upper part of the esophagus.
* Preoperative examination suggested that T4B was unresectable or distantly metastatic.
* Corticosteroids or other immunosuppressive drugs were used within 14 days before enrollment. Topical substitute steroids (daily dose ≤10mg) or short-term prescription corticosteroids (≤7 days) were allowed for the prevention or treatment of non-autoimmune diseases.
* A history of active autoimmune disease or a possible recurrence of autoimmune disease.
* Severe chronic or active infectious disease.
* History of interstitial lung disease.

Primary outcomes:
measure: Functional subsets of peripheral CD8 positive T cells
timeFrame: Approximately 1 years
measure: Overall response rate(ORR)
timeFrame: Approximately 1 years
measure: Pathological complete response (pCR)
timeFrame: At time of surgery
measure: Immune Related Adverse Events (irAEs)
timeFrame: Approximately 1 years
Secondary outcomes:
measure: Progress Free Survival(PFS)
timeFrame: Approximately 1 years
measure: 2-year survival rate
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
state: Sichuan
Study officials:
affiliation: Sichuan Cancer Hospital and Research Institute
name: Qiang Fang, PH.D
role: PRINCIPAL_INVESTIGATOR
References: