Neoadjuvant Platinum-based Chemotherapy for Patients With Resectable , Non-small Cell Lung Cancer With Switch to Chemotherapy Alternative in Nonresponders (NEOSCAN)
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.
Drug: pemetrexed plus cisplatin
Drug: vinorelbine and docetaxel
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|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)|
- response rate by FDG PET [ Time Frame: 2 years ] [ Designated as safety issue: No ](complete metabolic response + partial metabolic response) to alternative, non-platinum chemotherapy (vinorelbine + docetaxel) in patients with resectable Stage Ib-IIIa, NSCLC who do not respond to 2 cycles of platinum-based chemotherapy. The baseline for comparison for the primary endpoint is the PET scan performed immediately before the alternative chemotherapy.
- overall response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ](FDG PET and CT), rate of pathologic down-staging, rate of pathologic response, and stage-specific disease free and overall survival in patients with resectable Stage Ib-IIIa "non-squamous", NSCLC treated with neoadjuvant pemetrexed + cisplatin
- overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]DFS and OS will be calculated among patients evaluable for the primary objective. Followup for OS will start, at the time patients receive the first dose of vinorelbine + docetaxel, while for DFS it will start at the time of surgery.
- Evaluate the prognostic significance of radiographic response [ Time Frame: 2 years ] [ Designated as safety issue: No ]The sample size calculation is based on the ability to determine the objective response rate (CMR + PMR) to non-platinum chemotherapy (vinorelbine + docetaxel) in patients with resectable Stage IB-IIIA "non-squamous", NSCLC who do not respond to 2 cycles of pemetrexed + platinum (<35% change in SUVpeak on FDG PET by modified PERCIST criteria).
- Determine the safety and tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Safety and tolerability will be determined separately for the two neoadjuvant treatment regimens: pemetrexed + platinum and vinorelbine + docetaxel. Toxicity data (AEs, laboratory data and vital sign data) will be collected, tabulated according to CTCAE version 4.0 and summarized using descriptive statistics.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Experimental: pemetrexed plus cisplatin
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.
Drug: pemetrexed plus cisplatin
All enrolled pts will undergo baseline CT & FDG PET scan & imaging of the brain (MRI or CT). For all pts who undergo breath-hold PET/CT in addition to their free-breathing (FB) PET/CT scan, the FDG PET response assessment, which drives protocol decisions, will be derived from FB-PET studies only. Pts with non-squamous histology will be tx with pemetrexed 500 mg/m2 & cisplatin 75 mg/m2 delivered every 3 weeks for 2 cycles. Patients with squamous histology will be treated with gemcitabine 1250 mg/m2 on days 1 & 8 & cisplatin 75 mg/m2 on day 8 of a 21 day cycle or 2 cycles. Pts who are not eligible for cisplatin may receive carboplatin at AUC = 5 instead of cisplatin. Patients treated with carboplatin + gemcitabine must receive a lower starting dose of gemcitabine 1000 mg/m2. Following 2 cycles of platinum-based chemo, ps will undergo a repeat FDG PET and CT scan to measure treatment response. Responders will receive additional cycles of their first-line therapy with a goal of 4 cycles.
Experimental: vinorelbine and docetaxel
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: vinorelbine and docetaxel
Those who fail to respond 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01443078
|United States, New Jersey|
|Memoral Sloan Kettering Cancer Center|
|Basking Ridge, New Jersey, United States|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center @ Suffolk|
|Commack, New York, United States, 11725|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Memorial Sloan-Kettering at Mercy Medical Center|
|Rockville Centre, New York, United States|
|Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center|
|Sleepy Hollow, New York, United States, 10591|
|Principal Investigator:||Jamie E. Chaft, MD||Memorial Sloan Kettering Cancer Center.|