Icotinib and Arsenic Trioxide in Treating Non-small-cell Lung Cancer Patients With Resistance to EGFR-TKI

Study Overview
=================
Brief Summary
-----------------
The NSCLC patients who experienced good clinical responses to an EGFR-TKI will inevitably develop acquired resistance. A great deal of research are focusing on this issue. Arsenic trioxide showed efficacy and safety in acute promyelocytic leukemia, multiple myeloma and other solid tumors. Moreover, preclinical studies showed arsenic trioxide can reduce the resistance of tumor cells to chemotherapy and TKIs.

Official Title
-----------------
Phase I Study of the Combination of Icotinib and Arsenic Trioxide in Treating Non-small-cell Lung Cancer Patients With Resistance to EGFR-TKI

Conditions
-----------------
Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Icotinib
* Drug: Arsenic trioxide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed stage IIIB/IV lung cancer with EGFR mutation Progressed after platinum-based chemotherapy The last anti-tumor therapy before entering this study must be gefitinib, erlotinib or icotinib, and the duration for tumor response must be no less than 4 months, or the duration for stable disease must be no less than 6 months With a measurable disease with conventional CT) according to RECIST Criteria WHO performance status(PS)<= 2 N>=1.5×109/L, Plt>=1.0×109/L,Hb>=9g/dL; AST&ALT should <2.5ULN(without liver metastasis) or <5ULN(with liver metastasis).TBIL<=1.5ULN. Signed and dated informed consent before the start of specific protocol procedures. Exclusion Criteria: Allergic to icotinib or arsenic trioxide. Patients with metastatic brain tumors with symptoms. Severe systemic disease out of control such as unstable or uncompensated respiratory,cardiac,liver,renal diseases.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Icotinib and arsenic trioxide<br>Icotinib is administered 125 mg three times per day, until disease progression or untolerated toxicity. Arsenic trioxide is administered by intravenous injection with an initial dose of 4mg/m2 per day for day 1 to day 14 every 21 days. Three dose levels, 4mg/m2, 6mg/m2 and 8mg/m2 will be evaluated according to predefined dose escalation decision rules. The Maximum Administered Dose (MAD) was reached at the dose level when at least 2 patients developed a DLT. There was no further dose escalation when this dose was achieved. | Drug: Icotinib<br>* Icotinib is administered orally 125 mg three times per day, until disease progression or untolerated toxicity.<br>* Other names: Commana;Drug: Arsenic trioxide<br>* Arsenic trioxide is administered by intravenous injection with an initial dose of 4mg/m2 per day for day 1 to day 14 every 21 days. Three dose levels, 4mg/m2, 6mg/m2 and 8mg/m2 will be evaluated according to predefined dose escalation decision rules. The Maximum Administered Dose (MAD) was reached at the dose level when at least 2 patients developed a DLT. There was no further dose escalation when this dose was achieved.<br>* Other names: Arsenic trioxide for injection;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Serious and Non-Serious Adverse Events |  | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Up to 4 months | 
| Time to death |  | Up to 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Icotinib, Arsenic Trioxide, Resistance, Non-small cell lung cancer