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

Purpose

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.

Condition	Intervention	Phase
Lung Cancer	Drug: pemetrexed plus cisplatin Drug: vinorelbine and docetaxel	Phase 2


Study Type:	Interventional
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)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Nuclear Scans

Drug Information available for: Cisplatin Vinorelbine Docetaxel Vinorelbine tartrate Pemetrexed Pemetrexed disodium

U.S. FDA Resources

Further study details as provided by Memorial Sloan Kettering Cancer Center.:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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.


Estimated Enrollment:	100
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)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01443078

Locations


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

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center.

Eli Lilly and Company

Department of Defense

Investigators


Principal Investigator:	Jamie E. Chaft, MD	Memorial Sloan Kettering Cancer Center.

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided


Responsible Party:	Memorial Sloan Kettering Cancer Center.
ClinicalTrials.gov Identifier:	NCT01443078 History of Changes
Other Study ID Numbers:	11-106
Study First Received:	September 26, 2011
Last Updated:	November 18, 2014
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan Kettering Cancer Center.:


Carboplatin Cisplatin Pemetrexed (Altima) Taxotere (Docetaxel) Vinorelbine Tartrate (Navelbine)	Stage IB-III non squamous non-small cell lung cancer 11-106

Additional relevant MeSH terms:


Carcinoma, Non-Small-Cell Lung Lung Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms Cisplatin Docetaxel Pemetrexed Vinorelbine	Antimetabolites Antimetabolites, Antineoplastic Antimitotic Agents Antineoplastic Agents Antineoplastic Agents, Phytogenic Enzyme Inhibitors Folic Acid Antagonists Mitosis Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Radiation-Sensitizing Agents Therapeutic Uses Tubulin Modulators

ClinicalTrials.gov processed this record on February 25, 2015