Neoadjuvant LDRT Combined With Durvalumab in Potentially Resectable Stage III NSCLC
Status:
Recruiting
Trial end date:
2023-06-10
Target enrollment:
Participant gender:
Summary
Introduction: Although PACIFIC regimen definitive concurrent chemoradiotherapy (CRT) followed
by Durvalumab consolidation therapy is considered the standard of care for most of stage III
NSCLC patients, neoadjuvant immunotherapy combined with chemotherapy followed by surgery has
shown the trend to be considered for some potentially resectable patients. The rationales for
neoadjuvant treatment are tumor regression effect before surgery, early eradication of
micrometastasis. Recently the investigators also find some clinical trials exploring the
adding of 45 Gy in 25 fractions radiation to the combination of chemotherapy and
immunotherapy neoadjuvant therapy and the investigators could see the safety is the most
concern, especially the pneumonitis incidence. Low dose radiation could help control the
toxicity induced by radiation and has synergic effect with immunotherapy. The aim of this
phase Ib study is to assess the safety and feasibility of the combination of the concurrent
low dose radiation, chemotherapy and Durvalumab neoadjuvant therapy, to explore which
radiation dose is the best among our three-dose designs and evaluate if the combining
neoadjuvant therapy could further improve MPR in the meantime no severe toxicities especially
the grade 3-4 pneumonitis would happen.
Method: 9 eligible patients with histologically confirmed NSCLC (potentially resectable
clinical stage III according to the American Joint Committee on Cancer 8th staging system)
are enrolled. Patients receive Chemo (Day1 and 22 nanoparticle albumin-bound paclitaxel 260
mg/m2 and carboplatin AUC 5 ) and durvalumab (Day 1 and 22, 1500mg) and radiotherapy of 10 Gy
in 5 fractions, 20 Gy in 10 fractions, 30 Gy in 15 fractions respectively in our three groups
from Day1, followed by surgery. After surgery, patients are suggested to be treated with
durvalumab for one year (every 4weeks, 1500 mg). The primary endpoints are safety and
tolerability. The secondary endpoints are objective response rate (ORR), event-free survival
EFS), overall survival (OS), pathologic complete response (pCR), and major pathologic
response(MPR) in the primary tumor. biomarker analysis of PD-L1 using cancer tissue and LIPI,
ctDNA using blood sample will be conducted pre-and post- neoadjuvant and post-surgery.