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Pharmacogenomic & Phase II Study of Gemcitabine and Pemetrexed in Non-Small-Cell Lung Cancer.

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ClinicalTrials.gov Identifier: NCT00226577
Recruitment Status : Completed
First Posted : September 27, 2005
Results First Posted : January 12, 2011
Last Update Posted : March 23, 2017
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Eli Lilly and Company
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE September 23, 2005
First Posted Date  ICMJE September 27, 2005
Results First Submitted Date  ICMJE October 26, 2010
Results First Posted Date  ICMJE January 12, 2011
Last Update Posted Date March 23, 2017
Study Start Date  ICMJE February 2004
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2011)
Disease Response - Radiographic [ Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006 ]
Number of participants with partial or Complete Response. Complete response (CR) is defined as the total disappearance of all malignant and evaluable clinical evidence of cancer without the development of any new malignant lesions documented on the post chemotherapy chest CT and PET scan. Partial response (PR) (measurable disease only): When compared with pre-treatment measurements, a reduction of >30% in the sum of the largest diameters of all measurable lesions and absence of new lesions.
Original Primary Outcome Measures  ICMJE
 (submitted: September 23, 2005)
correlating molecular and genetic parameters to disease response
Change History Complete list of historical versions of study NCT00226577 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2011)
  • Disease Response - Pathologic [ Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006 ]
    Number of participants with Pathologic Complete Response. Pathologic complete response (pCR) is defined by a surgical pathology specimen, which consists of equal to or more than 95% fibrosis and necrosis.
  • Survival - Disease Free [ Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006 ]
    Disease-free survival (DFS) is defined as the period of time from surgery to the time when disease recurrence is clearly documented. A histologic confirmation is required in equivalent cases.
  • Survival - Overall [ Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006 ]
    Median range of number of participants with Overall Survival. Overall survival (OS) will be defined as the period of time from the first day of drug treatment to the date of death of the patient. Patients taken off study will be followed quarterly until death for survival data.
  • Toxicity [ Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006 ]
    Number of participants with toxicity ≥ Grade 3 after gemcitabine plus pemetrexed induction chemotherapy.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2005)
  • complete pathological response at surgery
  • disease-free survival
  • overall survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacogenomic & Phase II Study of Gemcitabine and Pemetrexed in Non-Small-Cell Lung Cancer.
Official Title  ICMJE Phase II Study of Neoadjuvant Chemotherapy With Gemcitabine and Pemetrexed in Resectable Non-Small-Cell Lung Cancer (NSCLC) With Pharmacogenomic Correlates.
Brief Summary This study will evaluate the efficacy and safety of chemotherapy given prior to having lung cancer surgically removed. Patients with resectable non-small cell lung cancer will receive gemcitabine and pemetrexed together for 4 times biweekly. Patients will be seen by a medical oncologist prior to each cycle of chemotherapy given. The medical oncologist will review patient's bloodwork and symptoms prior to approving next cycle of chemotherapy. All patients will then be evaluated with scans to determine response to chemotherapy and to determine if patient is a surgical candidate. These patients will then proceed to surgery to have the lung cancer removed. Follow up visits include bloodwork, scans, and a visit with the medical oncologist every three months for two years, then every six months for three years to monitor for disease recurrence.
Detailed Description

This study will evaluate the efficacy and safety of neoadjuvant chemotherapy with gemcitabine and pemetrexed given together 4-times biweekly in patients with resectable NSCLC. All patients will be seen by members of the Thoracic Oncology Program at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, and they will be discussed in our weekly multidisciplinary thoracic oncology conference. The conference includes pathologists, radiologists, thoracic surgeons, pulmonologists, radiation oncologists, medical oncologists, oncology nurse specialists, case managers, social workers, and clinical trials coordinators. They will have initial tests as outlined in the study timetable. Patients will receive gemcitabine biweekly on days 1, 15, 29, and 43 at a dose of 1,500 mg/m2. They will also receive pemetrexed at a dose of 500 mg/m2 on days 1, 15, 29, and 43. Gemcitabine will be given first over a period of 30 minutes i.v. followed by pemetrexed over 10 minutes i.v. All patients will get a post induction chemotherapy PET scan, CT scan, and PFT's including a DLCO. They will then go on to thoracotomy including bronchoscopy and mediastinal lymph node dissection between days 64 and 77 if the tumor is deemed completely resectable on restaging studies.

The administration of chemotherapy at the earliest time (neoadjuvant or induction chemotherapy) following diagnosis in an effort to reduce the risk of disease recurrence. This approach also allows for investigations of molecular parameters that may affect response to chemotherapy and patients' survival. It is our hypothesis that the expression of genes associated with activation, inactivation, and efficacy of the drugs gemcitabine and pemetrexed will predict response to therapy and prognosis. We further hypothesize that the expression of these genes will be altered during chemotherapy, and that the global assessment of tumor proliferation, apoptosis, and genome damage is associated with response to therapy. We propose a phase II study of neoadjuvant chemotherapy with gemcitabine and pemetrexed in patients with resectable NSCLC, specifically correlating molecular and genetic parameters to the primary clinical study endpoint disease response (radiographic CR+PR) and the secondary endpoints complete pathological response at surgery, disease-free survival, and overall survival.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer
Intervention  ICMJE
  • Drug: Gemcitabine
    Gemcitabine (GemzarR) 1500 mg/m2
    Other Name: Gemzar®
  • Drug: Pemetrexed
    Pemetrexed (AlimtaR) 500 mg/m2
    Other Name: Alimta®
  • Procedure: Surgery
    When the chemotherapy treatment is completed, the patient's tumor response will be evaluated by a CT scan, pulmonary function test, and another PET scan between days 50 and 63 (during weeks 8 and 9). If there is no growth or spread of the cancer on any of these tests, patients will then proceed to have surgery by week 10 to remove the cancer.
Study Arms  ICMJE Experimental: Pre-Surgery Chemotherapy
Interventions:
  • Drug: Gemcitabine
  • Drug: Pemetrexed
  • Procedure: Surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 13, 2010)
52
Original Enrollment  ICMJE
 (submitted: September 23, 2005)
80
Actual Study Completion Date  ICMJE December 2008
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Microscopically confirmed non-small cell carcinoma of the lung, which may be confirmed at the initial bronchoscopy and mediastinoscopy, or by transthoracic needle biopsy.
  • No prior therapy for lung cancer.
  • Patients must have disease stages IB (T2N0M0), IIA (T1N1M0), IIB (T2N1M0 and T3N0M0), or IIIA (T3N1M0 and T1-3N2M0). Patients with 2 lesions in one lobe (T4) (Stage IIIB) are eligible.
  • Patients must be deemed medically fit for surgical resection by a thoracic surgeon.
  • Patients must have an ECOG performance status of Zero or One.
  • Patients must have measurable or evaluable disease.
  • Measurable Disease: Any mass reproducibly measurable in one diameter (RECIST criteria).
  • Evaluable disease: Lesions apparent on chest CT, which do not meet the criteria for measurability. These include ill-defined masses associated with post obstructive changes.
  • Age >18 years.
  • Patient must be able to understand and sign the informed consent.
  • Patients must be >12 weeks from prior major surgery, such as a coronary artery bypass graft.

Exclusion Criteria:

  • White blood cell count <3000/mm3
  • Platelet count <100,000/mm3
  • Hemoglobin <9.0 g/dl
  • Creatinine >1.5 mg/dl
  • Total bilirubin >1.5 mg/dl
  • SGOT, SGPT, or AP >1.5 x upper limit of normal
  • Metastatic disease (except peribronchial/hilar lymph nodes=N1 and ipsilateral/subcarinal mediastinal lymph nodes=N2) or malignant pleural effusion detected on preoperative evaluation. Non-malignant effusions are cytology negative, are non-bloody, and are transudates. Effusions visible only on CT and not large enough for safe thoracentesis will not result in ineligibility. Exudative effusions, even if cytologically negative are excluded. Pleural fluid is considered exudative if: the ratio of pleural fluid protein to serum protein is >0.5 or the ratio of pleural fluid LDH to serum to serum LDH >0.6 or Pleural fluid LDH is >200 IU/liter. A staging PET scan will be used to exclude patients. If there are multiple areas of FDG uptake outside the area of the primary tumor and the hilar and ipsilateral mediastinal lymph nodes, the patient will be excluded by virtue of having metastatic disease. If however, only one area shows an increase in FDG uptake, the area of concern will need further evaluation such as a biopsy to exclude metastatic disease.
  • N3 lymph nodes (contralateral mediastinal/hilar and supraclavicular/scalene) or T4 primary tumor (malignant pleural effusion or mediastinal invasion) by clinical staging criteria (N3 as seen on CT or PET scan, which may be proven by mediastinoscopy at the investigators discretion).
  • Pregnancy.
  • Other active malignancy within 2 years with the exceptions of non-melanoma skin cancer and cervical carcinoma in situ.
  • Psychologic, familial, sociologic, or geographic conditions, which do not permit biweekly medical follow-up and adherence to the study protocol.
  • Prior radiation therapy for any cancer to the thorax.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00226577
Other Study ID Numbers  ICMJE MCC-13726
H3E-US-X009 ( Other Identifier: Eli Lilly & Company )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Eli Lilly and Company
Investigators  ICMJE
Principal Investigator: Gerold Bepler, M.D, Ph.D. H. Lee Moffitt Cancer Center (now at Karmanos Cancer Institute)
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date January 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP