Stereotactic Body Radiation Therapy (SBRT) in Newly Diagnosed Advanced Staged Lung Adenocarcinoma (Sindas) (Sindas)

Tyrosine-kinase Inhibitor （TKI） With or Without SBRT in Newly Diagnosed EGFRm Advanced Staged Lung Adenocarcinoma

To tested if the adding of consolidative SBRT to TKI in EGFR mutated patients with less than or equal to 5 metastatic sites (primary + 5) will improve progression free survival (PFS) compared to TKI alone.

Study Overview

• Status: Terminated
• Conditions: Stage IV EGFR Mutated Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: TKI (Gefitinib or Tarceva ); Radiation: Radiation: SBRT

Detailed Description

This protocol is a randomized phase III trial of TKI versus consolidative Stereotactic Body Radiation Therapy (SBRT) plus TKI for patients with Stage IV non-small cell lung cancer (NSCLC).

Prior to accrual on the trial, patients with Stage IV NSCLC will be tested with positive EGFR mutation. Patients who with fewer than or equal to 5 sites of oligometastatic disease will be randomized toTKI or consolidative SBRT to all sites of disease (followed by TKI at the medical oncologist's discretion). Choices of TKI will be determined by the medical oncologist based on clinical appropriateness.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 710062
      • Sichuan PPH, Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion):

  • all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology
  • all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion.
• No brain metastasis is allowed.
• Patients already started on erlotinib are eligible as long as their sites of disease are determined to be eligible for definitive local therapy by consensus of the principal investigators within 12 weeks of the patient first taking erlotinib.
• Lung adenocarcinoma histology confirmed
• Karnofsky Performance Status ≥ 70%

• 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) (except for patients with documented Gilbert's Syndrome)
  • 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

Exclusion Criteria:

• Treatment with TKI prior to developing metastatic disease
• Malignant pleural effusion or pleural disease
• Leptomeningeal disease or brain metastasis.
• Any site of disease that is not amenable to definitively local therapy including surgery or radiation therapy
• Women who are breastfeeding or pregnant
• Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment.
• Any medical co-morbidities that would preclude surgery or radiation therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TKI without SBRT; Newly diagnosed Patients will be placed on EGFR-TKI, ,Gefitinib 250mg po qd or Tarceva 150mg po qd for their metastatic EGFR-mutant stage IV oligometastatic disease. The oligometastatic disease will not receive SBRT	Drug: TKI (Gefitinib or Tarceva ); A first line TKI (Gefitinib 250mg po qd or Tarceva 150mg po qd ) will be administered according to the standard dosing of the drug for metastatic NSCL, no local therapy apply to oligo-metastatic sites.
Experimental: TKI with SBRT; experimental: Oligometastatic Non-Small Cell Lung Cancer Newly diagnosed patients will be placed on EGFR-TKI, Gefitinib 250mg po qd or Tarceva 150mg po qd, for their metastatic EGFR-mutant stage IV oligometastatic disease. All patients will TKI, Gefitinib 250mg po qd or Tarceva 150mg po qd, and SBRT at the same time. SBRT to up to 5 sites. The SBRT dose range from 5 Gy per fraction to 8 Gy per fraction. SBRT deliver within 5 fractions.	Drug: TKI (Gefitinib or Tarceva ); A first line TKI (Gefitinib 250mg po qd or Tarceva 150mg po qd ) will be administered according to the standard dosing of the drug for metastatic NSCL, no local therapy apply to oligo-metastatic sites.; Radiation: Radiation: SBRT; A first line TKI (Gefitinib 250mg po qd or Tarceva 150mg po qd ) will be administered according to the standard dosing of the drug for metastatic NSCL during a 1-week run-in period after which SBRT will be delivered to the all oligometastatic lesions concurrently with the TKI. The SBRT dose will be , ranging from at 25Gy (5 Gy per fraction) to 40 Gy (8 Gy per fraction).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Evaluate the effect of TKI with or without SBRT on progression free survival,to describe local control and out-of-field disease progression	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	To evaluate overall survival after SBRT followed by maintenance chemotherapy in comparison to maintenance chemotherapy alone.	4 years
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])	Using CTCAE system to evaluate toxicity profile	4 years

Collaborators and Investigators

• Sponsor: Sichuan Provincial People's Hospital
• Investigators: Study Chair: Ming Zeng, MD PhD, Sichuan Provincial People Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2016
• Primary Completion (Actual): August 30, 2020
• Study Completion (Actual): August 30, 2020

Study Registration Dates

• First Submitted: August 24, 2016
• First Submitted That Met QC Criteria: September 7, 2016
• First Posted (Estimate): September 8, 2016

Study Record Updates

• Last Update Posted (Actual): February 3, 2021
• Last Update Submitted That Met QC Criteria: January 29, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• 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; Erlotinib Hydrochloride; Gefitinib
• Other Study ID Numbers: 2016 15-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided