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

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

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.

Study Overview

• Status: Unknown
• Conditions: Lung Adenocarcinoma; EGFR Positive Non-small Cell Lung Cancer
• Intervention / Treatment: Radiation: Thoracic Hypofractionated Radiotherapy; Drug: EGFR-TKI

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:

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.

• Study Type: Interventional
• Enrollment (Anticipated): 76
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Radiation: Thoracic Hypofractionated Radiotherapy; 40-45 Gy/5-15f; Drug: EGFR-TKI; Gefitinib 250mg po qd or Erlotinib 150mg po qd or Icotinib 125mg po tid; Other Names: Gefitinib/Erlotinib/Icotinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the short-term quality of life (QOL)	FACT-E score at the 4 months after docetaxel consolidation therapy	4 months
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	We will assess the rate of symptomatic radiation pneumonitis in patients who received the radiation therapy.	1 years

Collaborators and Investigators

• Sponsor: First People's Hospital of Hangzhou

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: April 22, 2016
• First Submitted That Met QC Criteria: May 26, 2016
• First Posted (Estimate): June 2, 2016

Study Record Updates

• Last Update Posted (Estimate): June 2, 2016
• Last Update Submitted That Met QC Criteria: May 26, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Hypofractionated Radiotherapy; Lung Adenocarcinoma; EGFR Positive; Limited Metastases
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: HZCH-2016-08