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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Eli Lilly and Company
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01443078
First received: September 26, 2011
Last updated: August 27, 2014
Last verified: August 2014
  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:


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.

  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
Investigators
Principal Investigator: Jamie E. Chaft, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
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: August 27, 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:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Pemetrexed
Vinorelbine
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors
Folic Acid Antagonists
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 15, 2014