Neoadjuvant LDRT Combined With Durvalumab in Potentially Resectable Stage III NSCLC

Sponsor
Juan LI, MD
Study ID
NCT05157542
Phase
PHASE1
Status
Unknown

Conditions

  • Stage III Non-small Cell Lung Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — DRUG
    Day 1 and 22, 1500mg
  • nanoparticle albumin bound paclitaxel — DRUG
    Day1 and 22 nanoparticle albumin-bound paclitaxel 260 mg/m2 and carboplatin AUC 5
  • low dose radiation therapy — RADIATION
    10 Gy in 5 fractions, 20 Gy in 10 fractions, 30 Gy in 15 fractions respectively in our three groups from Day1

Study Details

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.

Key Dates

Start date
Jun 10, 2021
Status verified
Dec 2021
Primary completion
Jun 10, 2023
Completion
Jun 10, 2023

Study Design

Enrollment
9 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Arm
    Durvalumab 1500mg, IV, Q3W, 2 cycles Albumin paclitaxel 260 mg/m2 + Carboplatin AUC5, IV, Q3W, 2 cycles Chemoradiotherapy(CRT): Cohort 1: 2 Gy in 5 Fraction Cohort 2: 2 Gy in 10 Fraction Cohort 3: 2 Gy in 15 Fraction

Primary Outcome Measure

Incidence of treatment-emergent adverse events [ Time Frame: 30 days after last dose up to 36 months ]

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