Neoadjuvant Platinum-based Chemotherapy for Patients With Resectable , Non-small Cell Lung Cancer With Switch to Chemotherapy Alternative in Nonresponders (NEOSCAN)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test a new approach to the use of standard drugs before surgery in patients with lung cancer. This study will find out what effects, good and/or bad, that this approach has on the cancer. It is routine to give chemotherapy prior to surgery in patients with this type of lung cancer, to help keep it from coming back. It is also routine to perform a special type of scan called a PET scan. This PET scan measures how active a cancer is by use of a special tracer made out of sugar. In this study, all patients will have a PET scan and then be treated with standard chemotherapy drugs, either pemetrexed and cisplatin if the cancer is a non-squamous cancer or gemcitabine and cisplatin if the cancer is a squamous cancer. In rare cases, the doctor will decide to give carboplatin instead of cisplatin. In most patients, a repeat PET scan will show that the tumor is decreasing and they will complete standard chemotherapy then go on to have surgery. In some patients, a repeat PET scan will show that the tumor has not decreased enough. For these patients, the routine practice is to proceed with surgery. This research study will test whether switching from the standard treatment of pemetrexed and cisplatin or gemcitabine and cisplatin to a different treatment called vinorelbine and docetaxel is safe and effective. Vinorelbine and docetaxel are also standard chemotherapy drugs which work in a different way than pemetrexed or gemcitabine and cisplatin.

Official Title
-----------------
Phase II Trial of Neoadjuvant Platinum-based Chemotherapy for Patients With Resectable , Non-small Cell Lung Cancer With Switch to Chemotherapy Alternative in Nonresponders (NEOSCAN)

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Drug: pemetrexed
* Drug: cisplatin
* Drug: Carboplatin
* Drug: Gemcitabine Hydrochloride
* Drug: Vinorelbine Tartrate
* Drug: Docetaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathologic confirmation of NSCLC at MSKCC Stages IB, IIA, IIB, IIIA or IIIB NSCLC Primary tumor must measure ≥ 2 cm on CT imaging (per PERCIST guidelines) Primary tumor must be FDG-avid with an SUVmax >4.5 (to be consistent with PERCIST guidelines) Patients must be candidates for resection with curative intent Age ≥ 18 years Karnofsky performance status ≥ 70% Normal bone marrow function leukocytes ≥ 3,000/μl absolute neutrophil count ≥ 1,500/μl platelets ≥100,000/μl hemoglobin ≥9gm/dl. Adequate hepatic function Total bilirubin ≤1.5 x ULN AST ≤ 1.5 x UNL, ALT ≤ 1.5 x ULN Alkaline phosphatase ≤ 1.5x ULN Women of childbearing age must have a negative pregnancy test Men and women of childbearing potential must be willing to use effective contraception while on treatment and for at least 3 months thereafter Patients must have the ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients must not be receiving any other investigational agents History of myocardial infarction or unstable angina within the past 12 months Patients with peripheral neuropathy > grade 1 Other serious illness or medical condition including unstable cardiac disease requiring treatment, history of significant neurologic or psychiatric disorders (including psychotic disorders, dementia, or seizures), or active uncontrolled infection. Patients with diabetes mellitus requiring insulin therapy (per PERCIST guidelines) Patients with third space fluid which cannot be adequately controlled with drainage Women who are pregnant or breast-feeding Psychiatric illness or social situation that would limit compliance with study requirements Patients with known HIV infection requiring antiretroviral medications and those with AIDS Baseline subjective hearing deficit, even if it does not require a hearing aid or intervention, or interfere with activities of daily living (CTCAE grade 2 or higher) Baseline renal function <60 ml/min as calculated by the equation of Cockcroft and Gault using the patient's age, weight (kg), and serum creatinine (mg/dl). Congestive heart failure with New York Heart Association functional classification > II, characterized by fatigue, dyspnea or other symptoms which limit activities of daily life. Selection of Pemetrexed versus Gemcitabine: Patients treated with pemetrexed must meet all of the following criteria: Non-squamous histology Patients must have the ability to interrupt non-steroidal anti-inflammatory drugs (NSAIDs) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed Patients must have the ability to take folic acid, Vitamin B12, and dexamethasone according to protocol Patient refuses to take cisplatin

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: pemetrexed plus cisplatin, vinorelbine and docetaxel<br>This is a phase 2 clinical trial for patients with clinical Stage IB-III resectable and operable non-small cell lung cancer, evaluating whether the switch to an alternative, non-platinum neoadjuvant chemotherapy is safe and effective in patients who do not respond to neoadjuvant platinum-based chemotherapy. Those who fail to respond to platinum-based chemotherapy will be switched to the alternative neoadjuvant chemotherapy vinorelbine 45 mg/m2 and docetaxel 45 mg/m2 on day 1 followed by pegylated filgrastim on day 2, repeated every 2 weeks for 4 doses, followed by repeat FDG PET and CT scan. | Drug: pemetrexed<br> <br> Drug: cisplatin<br> <br> Drug: Carboplatin<br> <br> Drug: Gemcitabine Hydrochloride<br> <br> Drug: Vinorelbine Tartrate<br> <br> Drug: Docetaxel<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PERCIST Partial Metabolic Response | The primary endpoint was partial metabolic response after 2 cycles of switch therapy as assessed by PERCIST (SUVmax decrease ≥30% using the pre-switch scan as new baseline). | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Response Rate | The percentage of patients with a major pathologic response | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Carboplatin, Cisplatin, Pemetrexed (Altima), Taxotere (Docetaxel), Vinorelbine Tartrate (Navelbine), Stage IB-III, non squamous, non-small cell lung cancer, 11-106