Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Previously Treated Advanced Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
This research study examines the use of Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) in patients with lung cancer. Abraxane is a chemotherapy approved to treat patients with breast cancer. Doctors want to know if Abraxane is safe and effective in treating patients with lung cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) and epidermal growth factor receptor (EGFR) mutations.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To evaluate the overall response rate of weekly nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations following front-line therapy with EGFR tyrosine kinase inhibitors (TKI). SECONDARY OBJECTIVES: I. To evaluate the safety profile of weekly nab-paclitaxel in patients with advanced NSCLC with EGFR mutations following front-line therapy with an EGFR TKI. II. To evaluate the time-to-progression and overall survival. OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks and then every 3 months thereafter.

Official Title
-----------------
A Phase II Study of Weekly Abraxane for Patients With Advanced NSCLC With EGFR Mutations or With Durable Response to an EGFR Tyrosine Kinase Inhibitor Following Front Line Therapy With EGFR Tyrosine Kinase Inhibitors

Conditions
-----------------
Recurrent Non-Small Cell Lung Carcinoma, Stage IV Non-Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Other: Laboratory Biomarker Analysis
* Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathologically confirmed non-small cell lung cancer with documented EGFR mutation in tumor deoxyribonucleic acid (DNA) or complete/partial response to first line EGFR tyrosine kinase inhibitors with > or = to 6 months duration of response in patients who do not have a confirmed EGFR mutation At least one site of measurable disease as determined by the Investigator, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria Progressive disease with radiographic evidence of disease progression per investigator assessment during therapy with an EGFR tyrosine kinase inhibitor in the metastatic setting; patients may continue EGFR inhibitor therapy throughout the screening period until the day prior to nab-paclitaxel treatment initiation Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 at the time of informed consent Platelet count >= 100,000/uL Absolute neutrophil count >= 1,500/uL Hemoglobin >= 9 g/dL Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = < 2.5 times upper limit of normal Alkaline phosphatase =< 2.5 times upper limit of normal, unless bone metastasis is present in the absence of liver metastasis Bilirubin =< 1.5 mg/dL Creatinine =< 1.5 mg/dL Women of child-bearing potential (WOCP) and sexually active men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry, during treatment and for three months after completing treatment Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential Life expectancy of > 12 weeks Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment Exclusion Criteria: Prior conventional cytotoxic chemotherapy for metastatic or recurrent disease; prior adjuvant, neoadjuvant or chemoradiotherapy for NSCLC is permitted, provided at least 6 months elapsed prior to documented metastatic recurrence A single dose of a platinum doublet discontinued due to intolerability without evidence of disease progression is permitted Patient is < 5 years free of another primary malignancy, except: a) if the other malignancy is basal cell carcinoma or cervical carcinoma in situ or b) if the other primary malignancy is not considered clinically significant and is requiring no active intervention Progressive or symptomatic central nervous system (CNS) metastases; patients with known brain metastasis must have stable disease following treatment with surgery, radiation or both; in addition, they must be off corticosteroids Radiotherapy within 7 days of study treatment Peripheral neuropathy grade 2 or greater Grade III/IV congestive heart failure, as defined by New York Heart Association (NYHA) criteria, or myocardial infarction within 6 months Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study Patient has known chronic liver disease, e.g. diagnosis of chronic active hepatitis or cirrhosis Major surgery within 21 days of study treatment; minor surgery within 2 weeks of study treatment; placement of vascular access device and biopsies allowed and is not considered major or minor surgery Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent Pregnant or breast feeding females

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Treatment (paclitaxel albumin-stabilized nanoparticle formula)<br>Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation<br>* Given IV<br>* Other names: protein-bound paclitaxel;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (Complete and Partial Response) Defined by RECIST 1.1 Criteria | The response rate as the proportion and 95% confidence interval of patients who achieved a complete response or partial response will be calculated. | Assessed every two cycles from date of first study therapy until documented disease progression, date of death, unacceptable toxicity, or withdrawal of patient consent, whichever occurs first, assessed up to 60 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Percentage of Patients Experiencing Toxicity Within a Clinically Significant Category Defined as Neutropenia, Neutropenic Fever, or Neuropathy. | Toxicity rates will be described as percentage of patient who experienced a Grade 3 or higher clinically significant toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. | Collected from the time patient received the first dose of study therapy through 30 days following the last dose of study therapy or the start of a new cancer therapy, whichever occurred first, assessed up to 64 weeks. | 
| Overall Survival | Will report as median values with their respective 95% confidence intervals will be reported. Time to event distribution will be estimated using Kaplan-Meier method. | Assessed from date of patient consent until date of death from any cause or withdrawal of patient consent, whichever occurs first, assessed up to 305 weeks. | 
| Overall Percentage of Patients Experiencing Grade 3 or Higher Toxicity. | Toxicity rates will be described as percentage of patients experiencing Grade 3 or higher toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. | Collected from the time patient received the first dose of study therapy through 30 days following the last dose of study therapy or the start of a new cancer therapy, whichever occurred first, assessed up to 64 weeks. | 
| Time to Progression. | Reported as median values with their respective 95% confidence intervals for patients who were assessed. Time to event distribution will be estimated using the Kaplan-Meier method. | Assessed from date of patient consent until documented disease progression, date of death from any cause, start of new anti-cancer therapy, or withdrawal of patient consent, whichever occurs first, assessed up to 60 weeks. |