Pharmacogenomic & Phase II Study of Gemcitabine and Pemetrexed in Non-Small-Cell Lung Cancer.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Neoadjuvant Chemotherapy With Gemcitabine and Pemetrexed in Resectable Non-Small-Cell Lung Cancer (NSCLC) With Pharmacogenomic Correlates.|
- Disease Response - Radiographic [ Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006 ] [ Designated as safety issue: No ]
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.
- Disease Response - Pathologic [ Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]Number of participants with toxicity ≥ Grade 3 after gemcitabine plus pemetrexed induction chemotherapy.
|Study Start Date:||February 2004|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
|Experimental: Pre-Surgery Chemotherapy||
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00226577
|United States, Florida|
|H. Lee Moffitt Cancer Center & Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Gerold Bepler, M.D, Ph.D.||H. Lee Moffitt Cancer Center (now at Karmanos Cancer Institute)|