Trial Title:
CIETAI and Sequential Radiotherapy in Squamous Lung Cancer
NCT ID:
NCT05892237
Condition:
Carcinoma, Non-Small-Cell Lung
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Immunomodulating Agents
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
bronchial artery interventional therapy
Description:
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.
Arm group label:
central-type squamous NSCLC
Intervention type:
Drug
Intervention name:
Chemotherapy drug
Description:
Nano-paclitaxel 260 mg/m2, d1, ivgtt, q3w+Cisplatin 75mg/m2, d1, ivgtt,q3w.
Arm group label:
central-type squamous NSCLC
Intervention type:
Radiation
Intervention name:
IMRT
Description:
60Gy/2Gy/30f
Arm group label:
central-type squamous NSCLC
Intervention type:
Drug
Intervention name:
Immunotherapy
Description:
PD-1 inhibitor (Tirelizumab) 200mg, d1, ivgtt, 30-60min, q3w.
Arm group label:
central-type squamous NSCLC
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.
Detailed 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.
Criteria for eligibility:
Criteria:
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,
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:
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)
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).
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
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Daping Hospital, Third Military Medical University
Address:
City:
Chongqing
Zip:
400042
Country:
China
Status:
Recruiting
Contact:
Last name:
Dong Wang, PH.D.
Phone:
86-23-68757151
Email:
dongwang64@hotmail.com
Investigator:
Last name:
Dong Wang, PH.D.
Email:
Principal Investigator
Start date:
July 1, 2023
Completion date:
June 1, 2026
Lead sponsor:
Agency:
Dong Wang
Agency class:
Other
Source:
Third Military Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05892237
