NCT03727867

Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Combined With Early Stereotactic Body Radiation Therapy to the Primary Tumor in Advanced Non-small Cell Lung Cancer

Status unknown Phase 3 Last updated 30 January 2019

What this trial tests

Phase 3 trial testing Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Advanced Non-small Cell Lung Cancer in 300 participants. Status unknown.

Timeline

1 June 2019

Primary endpoint
1 June 2021

1 June 2022

Quick facts

Lead sponsor	Haihua Yang
Phase	Phase 3
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	300
Start date	1 June 2019
Primary completion	1 June 2021
Estimated completion	1 June 2022
Sites	1 location across China

Drugs / interventions tested

• Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor — full drug profile →
• Stereotactic Body Radiation Therapy — full drug profile →

Conditions studied

• Advanced Non-small Cell Lung Cancer — all drugs for Advanced Non-small Cell Lung Cancer →

Sponsor

Haihua Yang — full company profile →

Who can join

Adults 18 to 85, any sex, with Advanced Non-small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Non-small cell lung cancer (NSCLC) is a prevalent disease with high mortality and morbidity, particularly of adenocarcinoma in Asians. Fortunately, with the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), treatment of lung cancer usher in a new era, resulting in a hit of precise therapy and molecule sequencing. However, it is inevitable for patients to gain acquired resistance of EGFR TKI. Several studies have been demonstrated that there were approximately 30% heterogeneous cells in primary tumors. And emerging studies illuminated that main pattern of treatment failure was the recurrence of primary site. Moreover, it was proved that despite of the drug-resistance cells in progressive site, continual prescription of EGFR TKI in oligometastasis lung cancer could make a difference for patients in progression free survival (PFS) and overall survival (OS), owing to the residual responsive cells in another sites. Therefore, to explore an unique method to control heterogeneous cells in primary site so as to delay or prevent acquired resistance when taking EGFR TKI orally may be of great benefit and therapy.

It is known to all that stereotactic body radiation therapy (SBRT), with the advantage of hypofractionation and rapid release, succeed in several cancers, such as early lung cancer, prostatic, liver cancer and so on, for local control. Numerous reports explained SBRT played an irreplaceable role in progressive NSCLC patients after oral targeted medicine, regardless of EGFR or anaplastic lymphoma kinase (ALK) mutation. And the radiosensitivity of EGFR TKI in vitro and vivo may account for these inspiring results. What's more, it has reported that SBRT could induce inflammatory cell death, activate dendritic cell as well as accelerate antigen presentation in the draining lymph node, leading to antigen-specific adaptive immune response. Nevertheless, although the potential effects of SBRT on advanced NSCLC are obviously, few studies explore the preventive benefits of early SBRT combined with oral EGFR TKI on advanced lung cancer by eliminating the heterogeneous cells in primary site. In addition, the investigators' previous phase II study of SBRT combined with oral EGFR TKI had revealed its safety and potentially improvement of PFS for 6 months.

In this trial, the investigators put sight into assessing the efficacy of early application of SBRT to primary site in the advanced NSCLC patients and provide a hypothesis that early SBRT could strengthen the anti-tumor effect of EGFR TKI through eradicating the heterogenity of initial tumor cells.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Drug resistance of targeted therapy for advanced non-small cell lung cancer harbored EGFR mutation: from mechanism analysis to clinical strategy.
   Zhao Y, Wang H, He C. · · 2021 · cited 26× · PMID 34661758 · DOI 10.1007/s00432-021-03828-8
2. Systematic review of stereotactic body radiotherapy in stage III non-small cell lung cancer.
   Alcibar OL, Nadal E, Romero Palomar I, Navarro-Martin A. · · 2021 · cited 10× · PMID 33569334 · DOI 10.21037/tlcr-2020-nsclc-04
3. Prognostic implications of combining EGFR-TKIs and radiotherapy in Stage IV lung adenocarcinoma with 19-Del or 21-L858R mutations: A real-world study.
   Liang S, Wang H, Zhang Y, Tian H, et al · · 2024 · cited 4× · PMID 38659399 · DOI 10.1002/cam4.7208
4. Early stereotactic body radiation therapy improves progression-free survival of first-generation EGFR tyrosine kinase inhibitors in EGFR-mutated lung cancer: an observational cohort study.
   Xu H, Qi R, Zhou C, Yu Y, et al · · 2024 · cited 3× · PMID 39502405 · DOI 10.1177/17588359241290133