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

NCT ID: NCT02788058

Last Updated: 2016-06-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2022-05-31

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.

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.

Conditions

Lung Adenocarcinoma; EGFR Positive Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

EGFR-TKI

Patients take EGFR-TKI alone till tumor progression

Group Type: EXPERIMENTAL

EGFR-TKI

Intervention Type: DRUG

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

EGFR-TKI+hypofractionated radiotherapy

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

Group Type: ACTIVE_COMPARATOR

EGFR-TKI

Intervention Type: DRUG

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

Thoracic Hypofractionated Radiotherapy

Intervention Type: RADIATION

40-45 Gy/5-15f

Interventions

EGFR-TKI

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

Intervention Type: DRUG

Thoracic Hypofractionated Radiotherapy

40-45 Gy/5-15f

Intervention Type: RADIATION

Other Intervention Names

Gefitinib/Erlotinib/Icotinib

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First People's Hospital of Hangzhou

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Shenglin Ma, MD

Role: CONTACT

mashenglin@medmail.com.cn

0571-56007908 ext. 086

Other Identifiers

HZCH-2016-08

Identifier Type: -

Identifier Source: org_study_id