Clinical trial NCT03916913: TKI Followed by Thoracic Radiotherapy for Stage IV EGFR Mutant NSCLC
Official title: Tyrosine Kinase Inhibitor Followed by Thoracic Radiotherapy for Stage IV EGFR Mutant Non-small Cell Lung Cancer: A Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non-Small Cell Lung Cancer Metastatic
Keywords: Non small cell lung cancer
Oligo-metastasis
EGFR activating mutation
Radiotherapy
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
First posted: 2019-04-16
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this phase II trial with single arm, we aim to investigate the clinical efficacy and toxicity profile of local radiotherapy on all disease sites for EGFR-mutant oligo-metastatic NSCLC (no more than 3 metastatic lesions) who did not experience disease progression after at least 3 months of TKI therapy.

Detailed description: Tyrosine kinase inhibitor (TKI) has been widely accepted as the first-line therapy for stage IV NSCLC with active mutation of EGFR. Olio-metastasis is a disease status between localized and extended status of disease, namely with the limited number of lesions, which is generally defined as ≤ 5. A couple of phase II studies have shown that consolidation local management was able to prolong the local-regional tumor control and might further improve overall survival (OS) for oligo-metastatic NSCLC who have gained disease control from systemic therapy. However, there is lack of data regarding whether local radiotherapy (RT) could improve progression free survival (PFS) and OS for NSCLC with active EGFR mutation who have benefited from TKI. In this phase II trial with single arm, we aim to investigate the clinical efficacy and toxicity profile of local radiotherapy on all disease sites for EGFR-mutant oligo-metastatic NSCLC (no more than 3 metastatic lesions) who did not experience disease progression after at least 3 months of TKI therapy.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 and ≤75;
* ECOG performance status 0-1;
* Patients must provide study specific informed consent prior to study entry;
* Pathologically or cytologically diagnosed as NSCLC;
* EGFR activating mutation to TKI approved by histology, cytology or circulation tumor DNA;
* Stage IV NSCLC with ≤ 3 metastatic lesions (AJCC, 8th ed.) confirmed by meticulous radiographic examination. Brain MRI and 18F PET/CT is strongly recommended unless there is a contraindication;
* Patients have received≥3 months of TKI therapy and do not received disease progression;
* HB ≥ 10.0 g/dL;
* Absolute number of neutrophil granulocyte ≥ 1.5 × 109/L;
* Absolute number of PLT ≥ 100 × 109/L;
* Total bilirubin ≤ 1.5 folds of the maximum extent;
* ALT and AST ≤ 2.0 folds of the maximum extent;
* Cr ≤ 1.25 folds of the maximum extent and Ccr ≥ 60mLl/min.

Exclusion Criteria:

* Patients have received thoracic radiotherapy before;
* Malignant pleural effusion, pericardial effusion or peritoneal effusion;
* Patients have severe pulmonary comorbidity, such as ILD, COPD or other active pulmonary disease;
* Any unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, CHF (NYHA ≥ II), MI within 6 months of enrollment, severe arrhythmia requiring medication，hepatic, nephric or metabolic disease;
* HIV infection；
* Pregnancy or lactation women;
* ECOG status ≥2；
* Mixed SCLC component;
* Other factors that is considered ineligible.

Primary outcomes:
measure: Progression free survival
timeFrame: 1 year
Secondary outcomes:
measure: Overall response
timeFrame: 1 month after RT
measure: Overall survival
timeFrame: 2 year
measure: Time to progression of initial lesions
timeFrame: 1 year
measure: Time to appearance of new metastatic lesions
timeFrame: 1 year
measure: Treatment related toxicity
timeFrame: 1 year
measure: EORTC Quality of life
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital/Institute, Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: Cancer Hospital, CAMS
name: Jingbo Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: