Clinical trial NCT02893332: Stereotactic Body Radiation Therapy (SBRT) in Newly Diagnosed Advanced Staged Lung Adenocarcinoma (Sindas)
Official title: Tyrosine-kinase Inhibitor （TKI） With or Without SBRT in Newly Diagnosed EGFRm Advanced Staged Lung Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Stage IV EGFR Mutated Non-Small Cell Lung Cancer
Lead sponsor: Sichuan Provincial People's Hospital
Sponsor class: OTHER
First posted: 2016-09-08
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: 4 years
Secondary outcomes:
measure: Overall survival
timeFrame: 4 years
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])
timeFrame: 4 years
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Sichuan PPH, Cancer Center
state: Sichuan
Study officials:
affiliation: Sichuan Provincial People Hospital
name: Ming Zeng, MD PhD
role: STUDY_CHAIR
References: