Phase II Study of Neoadjuvant Chemotherapy With Gemcitabine and Pemetrexed in Resectable Non-Small-Cell Lung Cancer (NSCLC) With Pharmacogenomic Correlates.
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.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Disease Response - Radiographic
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.
06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
Gerold Bepler, M.D, Ph.D.
H. Lee Moffitt Cancer Center (now at Karmanos Cancer Institute)
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center & Research Institute||Tampa, Florida 33612|