Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Local Therapy in Advanced NSCLC With Non-progressive Disease (PD) After First Line Therapy

Summary: This is an open randomized control clinical study, which aims to investigate the overall benefit and safety of consolidative therapy in advanced NSCLC (stage III/IV) patients , who do not progress after front line systemic therapy (chemotherapy or target therapy).

Detailed description: It is required that pathological diagnosis and genetic profile including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1 (ROS1) be established prior to enrollment. Standard front line systemic should be given according to clinical practice. Molecular targeting drugs for patients with driving mutations should be acquired legally. Patients without driving mutations should undergo standard first line chemotherapy. One cycle is three weeks and response evaluation is done every two cycles. CR, PR and SD should be confirmed after four cycles of therapy.
  Patients, who achieve non-PD after four cycles of treatment, with distant metastasis involving no more than two organs and three total metastatic lesions, will be screened and then randomized into arm A or B if eligible.
  Arm A:
  Patient will be subject to local consolidative treatment to primary or metastases, which includes surgery, radiotherapy and interventional therapy. It is up to physicians' choice for standard maintenance or surveillance after LCT.
  Arm B:
  It is up to physicians' choice for standard maintenance or surveillance according to clinical practice.

Eligibility: Inclusion Criteria:
  -  Male or female, age >= 18 years, with life expectancy of at least 12 weeks.
  -  Patients with histologically documented, locally advanced or recurrent (stage III b and not amenable or combined modality treatment) or metastatic (stage IV) non-small cell lung cancer.
  -  Subjected to driving genes examination including EGFR, ALK and ROS1.
  -  Achieve complete response (CR)/partial response (PR)/stable disease (SD) after front line systemic treatment (chemotherapy or targeted therapy).
  -  Patients with stage I to III, who undergo radical therapy with disease-free survival (DFS) >12 months and then are given systemic anti-cancer therapy and achieve non-PD outcome.
  -  Distant metastasis involves no more than two organs and total metastatic lesions is limited to three.
  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of <= 2.
  -  Patients must have measurable disease according to the RECIST (version 1.1) criteria.
  -  Adequate organ function as defined by the following criteria:
  -  Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 upper limit of normal (ULN) in the absence of liver metastases or up to 5 ULN in case of liver metastases. Total bilirubin <= 1.5 ULN.
  -  Bone marrow function: Granulocyte count >= 1,500/mm3 and platelet count ≥100,000/mm3 and hemoglobin >= 90g/dl.
  -  Renal function: serum creatinine <= 1.5 ULN or creatinine clearance >= 60 ml/min. (based on modified Cockcroft-Gault formula).
  -  Adequate coagulating function.
  -  For all females of childbearing potential a negative serum/urine pregnancy test must be obtained within 48 hours before enrollment. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Males must agree to use effective contraception during the study period and for at least 12 weeks after completion of the study treatment.
  -  Written (signed) informed Consent to participate in the study.
  -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  Exclusion Criteria:
  -  Stage I-III a NSCLC completing radical treatment with DFS <= 12 months, then undergoing systemic anti-cancer treatment has no eligibility.
  -  Patients with history of any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).
  -  Prior palliative surgery or other local therapy specifically directed against advanced lung cancer.
  -  Contraindication for localized treatment including surgery, radiotherapy or interventional therapy judged by physicians.
  -  Patients with any unstable systemic disease (including active infections, significant cardiovascular disease, any significant hepatic, renal or metabolic disease).
  -  Patients who are at risk (in the investigator's opinion) of transmitting human immunodeficiency virus (HIV) through blood or other body fluids.
  -  Nursing or lactating women.
  -  Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
  -  Patients who has mental disorder or other disease that contribute to no compliance.
  -  Unwilling to write informed consent to participate in the study.
  -  Patients who is unwilling to accept the follow-up.

Relevance to patient case: possibly relevant