CIETAI and Sequential Radiotherapy in Squamous Lung Cancer

Last updated: August 22, 2023
Sponsor: Dong Wang
Overall Status: Active - Recruiting

Phase

2

Condition

N/A

Treatment

Chemotherapy drug

bronchial artery interventional therapy

Immunotherapy

Clinical Study ID

NCT05892237
2023108
  • Ages 18-80
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • 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, andM0 (according to the American Joint Committee on Cancer Staging (AJCC) 2017 Edition 8TNM Staging System). Central-type classified according to chest imaging orbronchoscopy.
  • 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 6months after adjuvant chemotherapy.
  • The main organ functions accorded with the following criteria within 7 days beforetreatment:
  1. 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.
  2. Biochemical tests should meet the following criteria: 1) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); 2) alanine aminotransferase (ALT) andaspartate aminotransferase (AST) ≤2.5 ULN, if accompanied by liver metastasis,ALT and AST ≤ 5 ULN; 3) serum creatinine (Cr) ≤ 1.5* ULN or creatinine clearancerate (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 whocould not provide new tissues could provide 5-8 paraffin sections of 3-5 μm byarchival preservation. Blood sample should be collected at a pre-specified time pointto complete the continuous dynamic MRD analysis. (non-mandatory).

Exclusion

Exclusion Criteria:

  • Severe allergic reactions to humanized antibodies or fusion proteins in the past.
  • Severe allergic reactions to component contained in contrast agent or granule embolismagent 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 otherform of immunosuppressive therapy within 14 days before the study, allowingphysiological doses of glucocorticoids (≤10mg/day prednisone or equivalent).
  • Patients with active, known or suspected autoimmune diseases. Patients with type Idiabetes, hypothyroidism requiring hormone replacement therapy, skin disordersrequiring no systemic treatment (such as vitiligo, psoriasis or alopecia). Patientswho would not triggers can be included.
  • Serious heart disease, include congestive heart failure, uncontrollable high-riskarrhythmia, unstable angina pectoris, myocardial infarction, and severe valvulardisease.
  • Patients received systemic antineoplastic therapy, including cytotoxic therapy, signaltransduction inhibitors, immunotherapy (or mitomycin C within 6 weeks before thegrouping),recieved over-extended-field radiotherapy (EF-RT) within 4 weeks before thegrouping or limited-field radiotherapy to evaluate the tumor lesions within 2 weeksbefore 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-rayexamination, sputum examination and clinical physical examination. Patients withactive pulmonary tuberculosis infection in the previous year should be excluded evenif they have been treated; Patients with active pulmonary tuberculosis infection morethan a year ago should also be excluded unless the course and type of antituberculosistreatment previously were appropriate.
  • Patients with brain metastases with symptoms or symptoms controlling less than 2months.

Study Design

Total Participants: 50
Treatment Group(s): 4
Primary Treatment: Chemotherapy drug
Phase: 2
Study Start date:
July 01, 2023
Estimated Completion Date:
June 01, 2026

Study Description

PD-1/PD-L1 immune checkpoint inhibitor (ICI), which has been introduced in the treatment of lung cancer, gastric cancer, colorectal cancer and other solid tumors, changed the strategy of cancer treatment. The more widely biomarkers for its efficacy include tumor PD-L1 proportional score (TPS), tumor mutation burden (TMB), DNA mismatch repair defect (dMMR), genomic instability (MSI-H) which were used to assess PD-L1 expression in tumor cells and the presence and density of T cells in the tumor microenvironment (TME). However, the overall efficacy of PD-1/PD-L1 remain unsatisfactory. To increase the concentration of PD-1/PD-L1 inhibitor in tumor and TME is a potential strategy to increase the efficacy. In this study, perfusion of PD-1/PD-L1 via bronchial arterial was harnessed to maximize the concentration of drugs in the tumor. We proposed a surgical procedure called Chemo-Immuno-embolization via Tumor Arterial Intervention (CIETAI). This study mainly included inoperable patients with central-type lung squamous cell carcinoma who received CIETAI at the initial treatment, followed by radiotherapy and PD-1/PD-L1 maintenance.

Connect with a study center

  • Daping Hospital, Third Military Medical University

    Chongqing, Chongqing 400042
    China

    Active - Recruiting

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