CIETAI and Sequential Radiotherapy in Squamous Lung Cancer

NCT05892237 | Recruiting Phase 2

• 1 other identifier: 2023108
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Central-type lung cancer refers to lung malignancies originating from the segmental bronchi and above. The most common tissue type is squamous cell carcinoma. Patients often present with cough, hemoptysis, hoarseness and also some critical conditions including superior vena caval obstruction syndrome. Therefore, effective treatment should be implemented as early as possible to rapidly reduce tumor burden and control the progression of the disease. Most of the central-type NSCLC are classified into T3-4, N1-2 stage and are non-resectable. The PACIFIC study changed the standard treatment model for inoperable locally advanced lung cancer with synchronous chemoradiotherapy and sequential PD-L1 immunotherapy. In clinical practice, Chinese patients often failed to finish concurrent chemoradiotherapy for high toxicity. In addition, combination with PD-1/PD-L1 inhibitors increased the risk of immune related pneumonia. Bronchial artery infusion (BAI), that directly infused drugs (chemo and PD-1 inhibitor) through tumor-nourishing arteries, has potential advantages in the treatment of central-type lung cancer. The drug concentration in tumor region increased to potentiate the antitumoral effect and also reduced the systemic adverse reactions. In this study, bronchial artery interventional therapy is conducted with precedence. The protocol for bronchial artery intervention includes infusion of chemo and PD-1 inhibitor followed by bronchial artery embolism (Chemo-Immulo-embolization via Tumor arterial, CIETAI). Followed CIETAI, two cycles of chemo/PD-1 therapy are planned to carried out before radiotherapy. After radiotherapy, maintenance PD-1 inhibitor are initiated for 1 year or until progression.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate 2 (ORR2)

  complete response(CR)+partial response(PR) according to RECIST 1.1

  2 year

Secondary Outcomes (7)

• Objective Response Rate 1 (ORR1)

  1 year

• Improvements of main symptoms after CITAI

  1 year

• Progression-free Survival(PFS)

  approximately 10 months

• Overall Survival（OS)

  approximately 18 months

• Toxicity

  the first date of treatment to 30 days after the last dose of study drug

Other Outcomes (3)

• Tumor proportion score (TPS) of PD-L1

  Baseline

• ctDNA MRD

  Baseline and 30 days after the last dose of study drug

• Surgery rate

  2 year

Study Arms (1)

central-type squamous NSCLC

EXPERIMENTAL

1\. Phase I: 1. Chemo-Immulo-embolization via Tumor Arterial, CIETAI: DSA guided tumor artery infusion of nano-paclitaxel 200 mg+PD-1 inhibitor (Tirelizumab) 200mg, followed by gelatin sponge particles (350-560um) embolization 2. two cycles of chemotherapy combined with immune checkpoint inhibitors (q3w): Nano-paclitaxel 260 mg/m2, d1, ivgtt; Cisplatin 75mg/m2, d1, ivgtt; PD-1 inhibitor (Tirelizumab) 200mg, d1, ivgtt, 30-60min 2. phase II: Chest radiotherapy: 60Gy/2Gy/30f 3. phase III: PD-1 inhibitor (Tirelizumab) 200mg, d1, ivgtt, 30-60min Maintenance for 1 year

Procedure: bronchial artery interventional therapy; Drug: Chemotherapy drug; Radiation: IMRT; Drug: Immunotherapy

Interventions

bronchial artery interventional therapy PROCEDURE

After successful anesthesia, right femoral artery puncture was performed by Seldinger method. 5F-Yashrio catheter is chosen to locate the bronchial artery of the diseased side at the level of the thoracic aortotracheal bifurcation. Angiography was performed (Osu 300mg/ml, 3ml/s, total 8ml, 200Psi) to visualize tumor blood supply artery before infusion of chemo+PD-1 inhibitor and embolism.

central-type squamous NSCLC

Chemotherapy drug DRUG

Nano-paclitaxel 260 mg/m2, d1, ivgtt, q3w+Cisplatin 75mg/m2, d1, ivgtt,q3w.

central-type squamous NSCLC

IMRT RADIATION

60Gy/2Gy/30f

central-type squamous NSCLC

Immunotherapy DRUG

PD-1 inhibitor (Tirelizumab) 200mg, d1, ivgtt, 30-60min, q3w.

central-type squamous NSCLC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients volunteered to participate in the study and signed the informed consent.
• Age 18-80, both male and female.
• Histologically or cytologically confirmed squamous lung cancer staging T3-4, Nany, and M0 (according to the American Joint Committee on Cancer Staging (AJCC) 2017 Edition 8 TNM Staging System). Central-type classified according to chest imaging or bronchoscopy.
• At least one measurable lesion according to RECIST 1.1.
• ECOG PS 0-1.
• Expected survival ≥ 6 months.
• Patients who never received systemic therapy in the past, including radiotherapy, chemotherapy, targeted therapy and immunotherapy, or patients who relapsed more than 6 months after adjuvant chemotherapy.
• The main organ functions accorded with the following criteria within 7 days before treatment:
• Blood routine examination ( without blood transfusion in 14 days): hemoglobin (HB) ≥ 90 g/L; neutrophil absolute value (ANC) ≥ 1.5 \*109/L; platelet (PLT) ≥80 \*109/L.
• Biochemical tests should meet the following criteria: 1) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); 2) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 \*ULN, if accompanied by liver metastasis, ALT and AST ≤ 5\* ULN; 3) serum creatinine (Cr) ≤ 1.5\* ULN or creatinine clearance rate (CCr) ≥ 60 ml/min;4) Serum albumin (≥35g/L). (3) Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥the low limit of normal value (50%).
• Tissue samples should be provided for biomarker analysis (such as PD-L1) Patients who could not provide new tissues could provide 5-8 paraffin sections of 3-5 μm by archival preservation. Blood sample should be collected at a pre-specified time point to complete the continuous dynamic MRD analysis. (non-mandatory).

You may not qualify if:

• Severe allergic reactions to humanized antibodies or fusion proteins in the past.
• Severe allergic reactions to component contained in contrast agent or granule embolism agent in the past.
• Metastasis to bone, brain, liver, pleural cavity, or any other distant organs.
• Diagnosed of immunodeficiency or received systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 14 days before the study, allowing physiological doses of glucocorticoids (≤10mg/day prednisone or equivalent).
• Patients with active, known or suspected autoimmune diseases. Patients with type I diabetes, hypothyroidism requiring hormone replacement therapy, skin disorders requiring no systemic treatment (such as vitiligo, psoriasis or alopecia). Patients who would not triggers can be included.
• Serious heart disease, include congestive heart failure, uncontrollable high-risk arrhythmia, unstable angina pectoris, myocardial infarction, and severe valvular disease.
• Patients received systemic antineoplastic therapy, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or mitomycin C within 6 weeks before the grouping),recieved over-extended-field radiotherapy (EF-RT) within 4 weeks before the grouping or limited-field radiotherapy to evaluate the tumor lesions within 2 weeks before the grouping.
• Positive hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus antibody (HCV Ab), indicating acute or chronic infection.
• Patients with active pulmonary tuberculosis (TB) infection judged by chest X-ray examination, sputum examination and clinical physical examination. Patients with active pulmonary tuberculosis infection in the previous year should be excluded even if they have been treated; Patients with active pulmonary tuberculosis infection more than a year ago should also be excluded unless the course and type of antituberculosis treatment previously were appropriate.
• Patients with brain metastases with symptoms or symptoms controlling less than 2 months.

Sponsors & Collaborators

• Dong Wang: lead

Study Sites (1)

Daping Hospital, Third Military Medical University

Chongqing, Chongqing Municipality, 400042, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Immunotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Central Study Contacts

Dong Wang, ph.D

CONTACT

+86-023-68757181; dongwang64@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: dean of clinical oncology (fomer)

Study Record Dates

• First Submitted: May 19, 2023
• First Posted: June 7, 2023
• Study Start: July 1, 2023
• Primary Completion: February 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 23, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)