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

• ClinicalTrials.gov Identifier: NCT05044728
• Recruitment Status: Recruiting
• First Posted: September 16, 2021
• Last Update Posted: September 16, 2021
• Sponsor: Sichuan Cancer Hospital and Research Institute
• Information provided by (Responsible Party): Qiang Fang,MD, Sichuan Cancer Hospital and Research Institute

Tracking Information

• First Submitted Date: September 3, 2021
• First Posted Date: September 16, 2021
• Last Update Posted Date: September 16, 2021
• Actual Study Start Date: April 1, 2021
• Estimated Primary Completion Date: April 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 5, 2021)

• Functional subsets of peripheral CD8 positive T cells [ Time Frame: Approximately 1 years ]
• Overall response rate(ORR) [ Time Frame: Approximately 1 years ]
  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.
• Pathological complete response (pCR) [ Time Frame: At time of surgery ]
  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.
• Immune Related Adverse Events (irAEs) [ Time Frame: Approximately 1 years ]
  Assess all adverse events according to the NCI Common Terminology Criteria for (NCI-CTCAE) v 4.0.3.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: September 5, 2021)

• Progress Free Survival(PFS) [ Time Frame: Approximately 1 years ]
  Progress Free Survival is defined as included the development of new metastases, or local progression of metastases or primary lesions that underwent surgical resection and will be assessed according to RESIST 1.1 criteria.
• 2-year survival rate [ Time Frame: up to 2 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.
• 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.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

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

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Non-small Cell Lung Cancer
• Esophageal Squamous Cell Carcinoma

Intervention

• Drug: Anti-PD-1 antibody combined with Paclitaxel and carboplatin.

  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.

• Procedure: Surgical treatment stage
  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.

Study Arms

Experimental: Neoadjuvant Chemotherapy Immunotherapy stage

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.

Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 5, 2021): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2023
• Estimated Primary Completion Date: April 1, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 72 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Qiang Fang, PH.D; +8618980758305; fq@sichuancancer.org

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05044728
• Other Study ID Numbers: CTIO1.0
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Qiang Fang,MD, Sichuan Cancer Hospital and Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Sichuan Cancer Hospital and Research Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Qiang Fang, PH.D; Sichuan Cancer Hospital and Research Institute

• PRS Account: Sichuan Cancer Hospital and Research Institute
• Verification Date: September 2021