Exploration of Immunodynamic Monitoring in the Population Evaluation of Neoadjuvant Chemotherapy Immunotherapy in Patients With Solid Tumors of the Chest.

NCT05044728 | Unknown Phase 2

• 1 other identifier: CTIO1.0
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer; Esophageal Squamous Cell Carcinoma

Keywords

Anti-PD-1; NSCLC; ESCC; Neoadjuvant; Immune microenvironment

Outcome Measures

Primary Outcomes (4)

• Functional subsets of peripheral CD8 positive T cells

  Approximately 1 years

• Overall response rate(ORR)

  Objective Response Rate is defined as complete response (CR) + partial response (PR), from the beginning of regimental therapy to the end of neoadjuvant therapy, the efficacy of baseline target lesions was assessed by RECIST 1.1 criteria.

  Approximately 1 years

• Pathological complete response (pCR)

  Pathological complete response is defined as 0% survival of tumor cells in surgically resected tumor samples after neoadjuvant therapy, as assessed by tumor regression grade.

  At time of surgery

• Immune Related Adverse Events (irAEs)

  Assess all adverse events according to the NCI Common Terminology Criteria for (NCI-CTCAE) v 4.0.3.

  Approximately 1 years

Secondary Outcomes (2)

• Progress Free Survival(PFS)

  Approximately 1 years

• 2-year survival rate

  up to 2 years

Study Arms (1)

Neoadjuvant Chemotherapy Immunotherapy stage

EXPERIMENTAL

Patients with locally advanced non-small cell lung cancer and locally advanced thoracic esophageal squamous cell carcinoma who met the entry and discharge criteria will be enrolled. After detecting the functional subsets of peripheral CD8-positive T cells, the group was randomly stratified 1:1, respectively. Group A received immunotherapy 24 hours after chemotherapy, and group B received chemotherapy 24 hours after immunotherapy.

Drug: Anti-PD-1 antibody combined with Paclitaxel and carboplatin.; Procedure: Surgical treatment stage

Interventions

Anti-PD-1 antibody combined with Paclitaxel and carboplatin. DRUG

Anti-PD-1 antibody, 240 mg, IV infusion for 30min (not less than 20min and not more than 60min), d1, every 3 weeks for total 2 cycles. Stratified regimen: group A, 24 hours after the end of chemotherapy; Group B will be given immunotherapy on the first day of each cycle. Paclitaxel, 135 mg/m2, IV, d1, q3w, for total 2 cycles. Carboplatin, AUC=5 (according to Calvert formula), IV, d1, every 3 weeks for a total of 2 cycles. Stratified regimen: group A, chemotherapy will be given on day 1 of each cycle; Group B will be given chemotherapy drugs 24 hours after the end of immunotherapy.

Neoadjuvant Chemotherapy Immunotherapy stage

Surgical treatment stage PROCEDURE

After the completion of neoadjuvant immunochemotherapy, patients will be tested again for the functional subsets of peripheral CD8 positive T cells. Alternative treatments will be sought for inoperable patients. For patients who are operable will receive minimally invasive or open surgery was performed 1 month after completion of neoadjuvant chemotherapy immunotherapy, and the functional subsets of peripheral CD8 positive T cells were detected again after surgery.

Neoadjuvant Chemotherapy Immunotherapy stage

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sichuan Cancer Hospital and Research Institute: lead

Study Sites (1)

Sichuan Cancer Hospital

Chengdu, Sichuan, 610000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Esophageal Squamous Cell Carcinoma

Interventions

Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Qiang Fang, PH.D

  Sichuan Cancer Hospital and Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qiang Fang, PH.D

CONTACT

+8618980758305; fq@sichuancancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Clinical Professor.

Model Details: This study is a prospective, single-arm, open cohort study (randomly stratified within the group).

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 16, 2021
• Study Start: April 1, 2021
• Primary Completion: April 1, 2022
• Study Completion: March 31, 2023
• Last Updated: September 16, 2021

Record last verified: 2021-09

Locations

CN (1)