Multi-center, Randomized, Double-blind, Placebo-controlled, Exploratory Study to Evaluate the Efficacy and Safety of HAD-B1 for Dose-finding in EGFR positive and locally advanced or metastatic NSCLC subjects who need Afatinib therapy

Recruitment & Eligibility

Status: Not yet recruiting

Sex: All

Target Recruitment: 66

Inclusion Criteria

1. Over 19-years-old;
2. Diagnosed with locally advanced or metastatic NSCLC who were unable to undergosurgery or radiation therapy;
3. Histologically or cytologically EGFR-positive, required afatinib therapy being failed or tolerated at least one cycle of erlotinib or gefitinib therapy;
4. With a lesion that can be measured by chest X-ray, CT or MRI with a single diameter or two diameters;
5. Eastern Cooperative Oncology Group (ECOG) performance status score 0 to 2;
6. Over six months life expectancy who have normal bone marrow function and solid organ function for more than 6 months;
- Bone marrow: ANC = 1.5x 109/L, platelet = 10x109/L, hemoglobin = 10g/dL
- Liver function: AST/ALT levels are below than 2 times of the normal upper limit
- Kidney function: creatinine levels are below than 2 times of the normal upper limit
7. Voluntarily sign a written informed consent in this trial.

Exclusion Criteria

1. Experienced severe drug hypersensitivity to a particular drug or hard to administer oral drug;
2. Currently pregnant or breastfeeding(Fertile women need adequate contraception during the study period);
3. Metastasized to the central nervous system or considered to need concurrent therapy, such as primary site radiation therapy, chemotherapy, or immunotherapy;
4. T790M (threonine-to-methionine amino acid change at position 790) of the EGFR kinase domain(acquired, rebiopsy) mutation-positive;
5. Other serious disease;
(a) Uncontrollable congestive heart failure or unstable angina, myocardial infarction within 1 year of study participation, uncontrollable hypertension or high-risk arrhythmia
(b) unable to understand the research content due to neurological or psychiatric disorders such as dementia and seizures
(c) Uncontrollable infections such as tuberculosis and hepatitis
6. A history of diagnosis or treatment of malignant tumors other than non-small cell lung cancer;
7. Participated in the combined administration of other drug research except for afatinib and other clinical trials within 2 weeks;
8. Needed to change the cycles of chemotherapy or dosing regimens other than cisplatin or Needed to change the cycles of radiation doses during radiotherapy;
9. Needed administration of immuno-inhibitors or platinum-based chemotherapy after PD-L1 expression test with multiple metastases with symptoms;
10. Should take prohibited-medication during this clinical trial;
11. Be judged to be unsuitable for this clinical trial by researcher.

Study & Design

Study Type: Interventional Study

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Comparison between two dose groups (0.972 g, 1.944 g) and placebo (0 g) at the end visit (visit 4, medication 12th week)

Secondary Outcome Measures

Name	Time	Method
Comparison between the two dose groups (0.972 g, 1.944 g) and the placebo group (0 g) at the visit 2(6 weeks) and end visit 4 ( 12 weeks) for evaluation of DCR(CR, PR, SD, PFS, TTP);Comparison between the two dose groups (0.972 g, 1.944 g) and the placebo group (0 g) at the visit 2(6 weeks) and end visit 4 ( 12 weeks) for evaluation of anemia and neutropenia(absolute neutrophil counts);Comparison between the two dose groups (0.972 g, 1.944 g) and the placebo group (0 g) at the visit 2(6 weeks) and end visit 4 ( 12 weeks) for evaluation of QOL and anti-fatigue questionnaire(EORTC QLQ-C30)