Back to resultsA Study of Hypofractionated Radiotherapy for Limited Metastatic NSCLC Harboring Sensitizing EGFR Mutations After First Line TKI Therapy
Primary Purpose
Lung Adenocarcinoma, EGFR Positive Non-small Cell Lung Cancer
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
EGFR-TKI
Thoracic Hypofractionated Radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Lung Adenocarcinoma focused on measuring Hypofractionated Radiotherapy, EGFR Positive, Lung Adenocarcinoma, Limited Metastases
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
EGFR-TKI
EGFR-TKI+hypofractionated radiotherapy
Arm Description
Patients take EGFR-TKI alone till tumor progression
After 3 mos TKI, patients with limited metastatic take EGFR-TKI concurrent with hypofractionated radiotherapy till tumor progression.
Outcomes
Primary Outcome Measures
Progression free survival
Secondary Outcome Measures
Frequency of T790M mutation before treatment detected by ctDNA
Abundance of T790M mutation before treatment detected by ctDNA
Frequency of T790M mutation after radiotherapy detected by ctDNA
Abundance of T790M mutation after radiotherapy detected by ctDNA
Frequency of T790M mutation after 1 year detected by ctDNA
Abundance of T790M mutation after 1 year detected by ctDNA
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.
To assess the short-term quality of life (QOL)
FACT-E score at the 4 months after docetaxel consolidation therapy
Full Information
NCT ID
NCT02788058
First Posted
April 22, 2016
Last Updated
May 26, 2016
Sponsor
First People's Hospital of Hangzhou
1. Study Identification
Unique Protocol Identification Number
NCT02788058
Brief Title
A Study of Hypofractionated Radiotherapy for Limited Metastatic NSCLC Harboring Sensitizing EGFR Mutations After First Line TKI Therapy
Official Title
A Phase II Trial of Hypofractionated Radiotherapy for Limited Metastatic NSCLC Harboring Sensitizing EGFR Mutations After First Line TKI Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Unknown status
Study Start Date
May 2016 (undefined)
Primary Completion Date
May 2021 (Anticipated)
Study Completion Date
May 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
First People's Hospital of Hangzhou
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Adenocarcinoma, EGFR Positive Non-small Cell Lung Cancer
Keywords
Hypofractionated Radiotherapy, EGFR Positive, Lung Adenocarcinoma, Limited Metastases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
76 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
EGFR-TKI
Arm Type
Experimental
Arm Description
Patients take EGFR-TKI alone till tumor progression
Arm Title
EGFR-TKI+hypofractionated radiotherapy
Arm Type
Active Comparator
Arm Description
After 3 mos TKI, patients with limited metastatic take EGFR-TKI concurrent with hypofractionated radiotherapy till tumor progression.
Intervention Type
Drug
Intervention Name(s)
EGFR-TKI
Other Intervention Name(s)
Gefitinib/Erlotinib/Icotinib
Intervention Description
Gefitinib 250mg po qd or Erlotinib 150mg po qd or Icotinib 125mg po tid
Intervention Type
Radiation
Intervention Name(s)
Thoracic Hypofractionated Radiotherapy
Intervention Description
40-45 Gy/5-15f
Primary Outcome Measure Information:
Title
Progression free survival
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Frequency of T790M mutation before treatment detected by ctDNA
Time Frame
1 months
Title
Abundance of T790M mutation before treatment detected by ctDNA
Time Frame
1 months
Title
Frequency of T790M mutation after radiotherapy detected by ctDNA
Time Frame
3 months
Title
Abundance of T790M mutation after radiotherapy detected by ctDNA
Time Frame
3 months
Title
Frequency of T790M mutation after 1 year detected by ctDNA
Time Frame
1 year
Title
Abundance of T790M mutation after 1 year detected by ctDNA
Time Frame
1 year
Title
Rate of CTCAE grade 2 or higher radiation pneumonitis
Description
We will assess the rate of symptomatic radiation pneumonitis in patients who received the radiation therapy.
Time Frame
1 years
Title
To assess the short-term quality of life (QOL)
Description
FACT-E score at the 4 months after docetaxel consolidation therapy
Time Frame
4 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shenglin Ma, MD
Phone
0571-56007908
Ext
086
Email
mashenglin@medmail.com.cn
12. IPD Sharing Statement
Learn more about this trial
A Study of Hypofractionated Radiotherapy for Limited Metastatic NSCLC Harboring Sensitizing EGFR Mutations After First Line TKI Therapy
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