A Study of Hypofractionated Radiotherapy for Limited Metastatic NSCLC Harboring Sensitizing EGFR Mutations After First Line TKI Therapy

Sponsor

First People's Hospital of Hangzhou (Other)

Overall Status

Unknown status

CT.gov ID

NCT02788058

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

To evaluate the efficacy and toxicity of patients treated with hypofractionated radiotherapy for limited metastatic NSCLC harboring sensitizing EGFR mutations after first line TKI therapy. An exploratory biomarker analysis in blood and tumor samples is also planned.

Condition or Disease	Intervention/Treatment	Phase
Lung Adenocarcinoma EGFR Positive Non-small Cell Lung Cancer	Drug: EGFR-TKI Radiation: Thoracic Hypofractionated Radiotherapy	Phase 2

Detailed Description

Rational:

After inductive TKI therapy in NSCLC with sensitizing EGFR mutations, the residual lesion might be the source of subsequent disease progression, defined as acquired resistance to TKI. Two reasons can be used to explain the formation of the residual lesion：1）there is a subgroup of cancer cells that are not sensitive to TKI therapy because of tumor heterogeneity, like de novo T790M mutation; 2)some cancer cells can keep static state during the beginning treatment, and then develops acquired resistance to TKI therapy under the long-term drug pressure and continue to re-proliferation. From this point of view, elimination of residual lesion provides the chance to reduce or slow the possibility of developing resistance to TKI.

Objective:

Study Design

Study Type:

Interventional

Anticipated Enrollment :

76 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial of Hypofractionated Radiotherapy for Limited Metastatic NSCLC Harboring Sensitizing EGFR Mutations After First Line TKI Therapy

Study Start Date :

May 1, 2016

Anticipated Primary Completion Date :

May 1, 2021

Anticipated Study Completion Date :

May 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EGFR-TKI Patients take EGFR-TKI alone till tumor progression	Drug: EGFR-TKI Gefitinib 250mg po qd or Erlotinib 150mg po qd or Icotinib 125mg po tid Other Names: Gefitinib/Erlotinib/Icotinib
Active Comparator: EGFR-TKI+hypofractionated radiotherapy After 3 mos TKI, patients with limited metastatic take EGFR-TKI concurrent with hypofractionated radiotherapy till tumor progression.	Drug: EGFR-TKI Gefitinib 250mg po qd or Erlotinib 150mg po qd or Icotinib 125mg po tid Other Names: Gefitinib/Erlotinib/Icotinib Radiation: Thoracic Hypofractionated Radiotherapy 40-45 Gy/5-15f

Arm

Intervention/Treatment

Experimental: EGFR-TKI

Patients take EGFR-TKI alone till tumor progression

Drug: EGFR-TKI

Gefitinib 250mg po qd or Erlotinib 150mg po qd or Icotinib 125mg po tid

Other Names:

Gefitinib/Erlotinib/Icotinib

Active Comparator: EGFR-TKI+hypofractionated radiotherapy

After 3 mos TKI, patients with limited metastatic take EGFR-TKI concurrent with hypofractionated radiotherapy till tumor progression.

Drug: EGFR-TKI

Gefitinib 250mg po qd or Erlotinib 150mg po qd or Icotinib 125mg po tid

Other Names:

Gefitinib/Erlotinib/Icotinib

Radiation: Thoracic Hypofractionated Radiotherapy

40-45 Gy/5-15f

Outcome Measures

Primary Outcome Measures

Progression free survival [3 years]

Secondary Outcome Measures

Frequency of T790M mutation before treatment detected by ctDNA [1 months]
Abundance of T790M mutation before treatment detected by ctDNA [1 months]
Frequency of T790M mutation after radiotherapy detected by ctDNA [3 months]
Abundance of T790M mutation after radiotherapy detected by ctDNA [3 months]
Frequency of T790M mutation after 1 year detected by ctDNA [1 year]
Abundance of T790M mutation after 1 year detected by ctDNA [1 year]
Rate of CTCAE grade 2 or higher radiation pneumonitis [1 years]
We will assess the rate of symptomatic radiation pneumonitis in patients who received the radiation therapy.
To assess the short-term quality of life (QOL) [4 months]
FACT-E score at the 4 months after docetaxel consolidation therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Newly diagnosed metastatic lung adenocarcinoma harboring sensitizing EGFR mutations (L858R, exon 19 deletion), and became oligometastatic disease after 3 months TKI, evaluated by PET/CT scan, brain MRI, and abdomen ultrasound (≤6 discrete lesions of disease, exclusive of the brain metastases, ≤3 lesions in the liver, ≤3 lesions in the lung);
All sites of disease must be amenable to definitive RT;
An intrathoracic lymph nodal station is considered 1 discrete lesion, according to IASLC lymph nodal station map;
Age 18 years or older;
ECOG Performance Status 0-2;
Adequate bone marrow, liver and renal function, as specified below: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L; Hemoglobin ≥ 8 g/dL; Platelets ≥ 100 x 109/L; Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) ; AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present; Serum creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal;
For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment;
Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 3 months thereafter;
Patients and their family signed the informed consents;

Exclusion Criteria:

Received chemotherapy before TKI therapy;
Brain parenchyma or leptomeningeal disease;
Any site of disease that is not amenable to definitive RT;
Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment;
Any medical co-morbidities that would preclude radiation therapy.