Study of Abraxane and Carboplatin to Treat Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
This is a phase II trial of abraxane and carboplatin in extensive stage small cell lung cancer to examine overall response rate, time to progressive disease, survival time, and assessment of toxicity profile for Carboplatin and Abraxane.

Detailed Description
-----------------
Patients are being asked to be in this study because they have extensive disease small cell lung cancer. All eligible participants who agree to be in the study will receive both abraxane and carboplatin. The researchers want to evaluate the activity and safety of the combination of abraxane and carboplatin, and if this combination can help people with extensive disease small cell lung cancer. Carboplatin is a chemotherapy drug that has been approved by the Food and Drug Administration (FDA) to treat ovarian cancer. It is in a class of drugs known as platinum-containing compounds. It slows or stops the growth of cancer cells in your body. Carboplatin is not approved by the FDA for use in the treatment of small-cell lung cancer, either alone or combined with other anti-cancer drugs. However, carboplatin given with paclitaxel is a standard or active treatment in patients with small cell lung cancer, non-small cell lung cancer, breast cancer, and ovarian cancer. Abraxane is a chemotherapy drug that was approved by the FDA to treat metastatic breast cancer after other chemotherapy has already been tried. Abraxane is a new preparation of the active ingredient in the chemotherapy drug, paclitaxel. In a study done in breast cancer patients, Abraxane was compared to paclitaxel. Abraxane has been shown to be more effective than paclitaxel in tumor response and tumor progression, in addition to having fewer side effects than paclitaxel. Abraxane was shown to cause less damage to a person's white blood cells (the cells that fight infection) and cause fewer allergic reactions; however, more patients developed numbness of their hands and feet. Carboplatin and Abraxane are intravenous (IV) medications. Patients will begin treatment with 2 cycles (1 cycle = 21 days) of abraxane and carboplatin. Then there will be a disease assessment at cycles 2 and 4. Patients with stable disease, partial response, or complete response will get additional cycles. Patients with progressive disease no will be taken off the study treatment. A maximum of 6 cycles will be given.

Official Title
-----------------
Phase II Clinical Trial of Carboplatin and Abraxane in Patients With Extensive Stage Small Cell Lung Cancer

Conditions
-----------------
Small Cell Lung Cancer

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histological or cytological diagnosis of extensive stage small-cell lung cancer (ES-SCLC),* including malignant pleural effusion Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 No prior systemic chemotherapy, immunotherapy, or biological therapy for SCLC Measurable disease as defined by the RECIST criteria Adequate organ function as defined by the protocol Female patients of child bearing potential (CBP) must agree to use of reliable method of birth control during and for 3 months following treatment Patients must sign informed consent document Patients must be ≥ 18 years of age Patients with brain metastases that have been adequately treated and are determined to be controlled by the attending physician are eligible Patients who have had prior malignancies are eligible if they are ≥ 5 years from diagnosis free of disease or the attending physician believes the patient's prognosis is best defined by the ES-SCLC (if questions concerning this eligibility criteria arise, please contact the principal investigator) (*)ES-SCLC defined as metastases outside the chest, pulmonary metastases, or contralateral metastases (supraclavicular or hilar) nodes that could not be included with a reasonable single radiation port. Patients with malignant pleural effusions are considered extensive stage. Exclusion Criteria: Received treatment within the last 30 days with a drug that has not received Food and Drug Administration (FDA) approval for any indication at the time of study entry Pregnancy or breast feeding Serious active infection that would require a prolonged course (4-6 weeks) of antibiotics or would compromise the safety of the patient or compromise the patient's ability to complete the study Symptomatic brain metastases Grade ≥ 2 neuropathy using NCI CTCAE version 3.0 criteria Previous anaphylactic reaction to carboplatin, paclitaxel, and docetaxel Severe or uncontrolled cardiac disease, defined as uncontrolled or unstable angina, myocardial infarction in the last month, uncontrolled congestive heart failure (≥ 3 admissions for congestive heart failure in the 3 months prior to diagnosis)

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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Carboplatin + Abraxane (240mg/m2) on Day 1 of a 21 Day cycle, up to 6 cycles | Drug: Carboplatin<br>* Carboplatin will be given at a dose of target area under the concentration versus time curve in mg/mL•min (AUC)=6, on Day 1 of a 21 Day Cycle<br>* Other names: Paraplatin;Drug: Abraxane<br>* Abraxane will be given at a dose of 240mg/m2 on Day 1 of a 21 Day Cycle (Arm A) Abraxane will be given at a dose of 80mg/m2 on Days 1, 8, and 15 of a 21 Day Cycle (Arm B)<br>* Other names: Paclitaxel;|
| Experimental: Arm B<br>Carboplatin + Abraxane (80mg/m2)given on Days 1, 8 and 15 of a 21 Day Cycle, up to 6 cycles | Drug: Carboplatin<br>* Carboplatin will be given at a dose of target area under the concentration versus time curve in mg/mL•min (AUC)=6, on Day 1 of a 21 Day Cycle<br>* Other names: Paraplatin;Drug: Abraxane<br>* Abraxane will be given at a dose of 240mg/m2 on Day 1 of a 21 Day Cycle (Arm A) Abraxane will be given at a dose of 80mg/m2 on Days 1, 8, and 15 of a 21 Day Cycle (Arm B)<br>* Other names: Paclitaxel;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Radiological imaging should be performed every 12 weeks, to ascertain the overall (or objective) response rate (Complete Response or Partial Response) according to the RECIST guidelines. Complete Response (CR) - Disappearance of all target lesions. Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Overall Response Rate = CR+PR. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year Overall Survival (OS) | Percentage of participants from the start of treatment with the disease that are still alive. | every 12 weeks for 1 year | 
| Progression Free Survival (PFS) | Defined as the time between trial enrollment to disease progression or death (whichever occurs first) or date of last contact | Through the end of the study, an average of approximately 8 months | 
| Number of Individuals With Adverse Events | Drug toxicities will be evaluated during treatment period and 30 days post treatment. Toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE 3.0) criteria. Grade 3 or 4 adverse events were reported | 10 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lung cancer, Small cell lung cancer, Abraxane, Paclitaxel, Carboplatin, Phase II, Randomized, Lineberger, LCCC