Phase II Study of Abraxane and Gemicitabine in Patients With Advanced Adenocarcinoma Non-Small Cell Lung Cancer Progressing After First-Line Platinum-Based Chemotherapy

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to see how well the combination of Abraxane and gemcitabine works in people with advanced adenocarcinoma NSCLC who have already had treatment for their disease. Gemcitabine and Abraxane are FDA approved chemotherapies; however, the FDA has not approved this combination in the treatment of this specific type of cancer. Patients may continue to receive the study drugs until their disease gets worse or they have unacceptable side effects.

Official Title
-----------------
Phase II Study of Abraxane and Gemicitabine in Patients With Advanced Adenocarcinoma Non-Small Cell Lung Cancer Progressing After First-Line Platinum-Based Chemotherapy

Conditions
-----------------
Patients With Stage IV or Recurrent Adenocarcinoma of the Lung

Intervention / Treatment
-----------------
* Drug: Abraxane
* Drug: Gemcitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologic or cytologic diagnosis of adenocarcinoma non-small cell lung cancer Stage IV non-small cell lung cancer or recurrent disease which cannot be approached with curative intent. First-line treatment with a standard platinum doublet chemotherapy regimen (carboplatin or cisplatin at standard dosing plus one of the following drugs at standard dosing: paclitaxel, docetaxel, vinblastine, vinorelbine, pemetrexed, or etoposide). Patients who received platinum-based chemotherapy for localized lung cancer (either adjuvant chemotherapy following surgery or chemotherapy given in conjunction with definitive radiation) are eligible if their cancer has recurred within 6 months of platinum-based chemotherapy. Must have recovered from toxic effects of prior chemotherapy ECOG performance status of 0-1 Life expectancy of at least 12 weeks Age 18 or greater Must have measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded as > 20 mm with conventional techniques or > 10 mm with spiral CT scanning). Patients with prior malignancies are allowed, provided they have been treated with curative intent and have no evidence of active disease. Patients must be capable of giving informed consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing. Bilirubin < 1.5 mg/dL Patients must have adequate liver function: AST and ALT < 2.5 X upper limit of normal, alkaline phosphatase < 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis Patients must have adequate bone marrow function: Platelets >100,000 cells/mm3, Hemoglobin > 9.0g/dL and ANC > 1,500 cells/mm3 Patients must have adequate renal function: creatinine <1.5 mg/dL Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment Negative serum β-hCG pregnancy test at screening for patients of childbearing potential. Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE) Exclusion Criteria: Patients with EGFR or EML4-ALK mutations ECOG performance status >1 Patients previously treated with gemcitabine or Abraxane Uncontrolled intercurrent illness including, but not limited to: uncontrolled ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Known HIV or Hepatitis C Untreated central nervous system metastases. Patients are eligible if they are clinically stable, off all steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radio surgery) ending at least 2 weeks prior to enrollment, or after surgical resection performed at least 2 weeks prior to enrollment. Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent Pregnant or breast-feeding patients, as chemotherapy is thought to present substantial risk to the fetus/infant. Men and women of reproductive potential may not participate in this study unless they have agreed to use an effective contraceptive method while in this study. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients must agree to continue contraception for 3 months from the date of the last study drug administration

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
Interventional Model Description: a prospective, single-arm, non-randomized, phase II trial designed to evaluate the efficacy of combination gemcitabine and albumin-bound paclitaxel for advanced adenocarcinoma non-small cell lung cancer progressing after first-line platinum-based chemotherapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemcitabine + Paciltaxel<br>All patients were treated intravenously with albumin-bound paclitaxel at 100 mg/m2 plus gemcitabine at 1000 mg/m2 on days 1 and 8 of each three-week cycle. | Drug: Abraxane<br> <br> Drug: Gemcitabine<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | The percentage of patients with a Partial Response or Complete Response recorded from the start of the treatment until disease progression/recurrence by RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the diameter of target lesions; Overall Response (OR) = CR + PR. | Averaging about 16 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Measures the length of time from the first day of therapy until Progressive Disease, death from any cause, or last patient contact. Disease Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Averaging about 16 weeks | 
| Overall Survival | Length of time from the first day of therapy to death from any cause or last patient contact | Averaging about 47 weeks | 
| Disease Control Rate | The percentage of patients with a Partial Response, a Complete Response, or Stable Disease during the study. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the diameter of target lesions; Overall Response (OR) = CR + PR. | The duration of study treatment, averaging about 16 weeks. |