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

Lung Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02788058
• Other study ID #: HZCH-2016-08
• Status: Not yet recruiting
• Phase: Phase 2
• First received: April 22, 2016
• Last updated: May 26, 2016
• Start date: May 2016
• Est. completion date: May 2022

Study information

• Verified date: May 2016
• Source: First People's Hospital of Hangzhou
• Contact: Shenglin Ma, MD
• Phone: 0571-56007908
• Email: mashenglin[@]medmail.com.cn
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 76
• Est. completion date: May 2022
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Non-Small-Cell Lung
• EGFR Positive Non-small Cell Lung Cancer
• Lung Adenocarcinoma
• Lung Neoplasms

Intervention

Drug:
• EGFR-TKI
Gefitinib 250mg po qd or Erlotinib 150mg po qd or Icotinib 125mg po tid

Radiation:
• Thoracic Hypofractionated Radiotherapy
40-45 Gy/5-15f

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
First People's Hospital of Hangzhou

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		3 years	No
Secondary	Frequency of T790M mutation before treatment detected by ctDNA		1 months	No
Secondary	Abundance of T790M mutation before treatment detected by ctDNA		1 months	No
Secondary	Frequency of T790M mutation after radiotherapy detected by ctDNA		3 months	No
Secondary	Abundance of T790M mutation after radiotherapy detected by ctDNA		3 months	No
Secondary	Frequency of T790M mutation after 1 year detected by ctDNA		1 year	No
Secondary	Abundance of T790M mutation after 1 year detected by ctDNA		1 year	No
Secondary	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	No
Secondary	To assess the short-term quality of life (QOL)	FACT-E score at the 4 months after docetaxel consolidation therapy	4 months	No