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Phase II Study of Neoadjuvant Chemotherapy With Gemcitabine and Pemetrexed in Resectable Non-Small-Cell Lung Cancer (NSCLC) With Pharmacogenomic Correlates.

Phase 2
18 Years
Not Enrolling
Lung Cancer

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Trial Information

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.

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

- 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

- Evaluable disease: Lesions apparent on chest CT, which do not meet the criteria for
measurability. These include ill-defined masses associated with post obstructive

- 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

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease Response - Radiographic

Outcome Description:

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.

Outcome Time Frame:

06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006

Safety Issue:


Principal Investigator

Gerold Bepler, M.D, Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center (now at Karmanos Cancer Institute)


United States: Food and Drug Administration

Study ID:




Start Date:

February 2004

Completion Date:

December 2008

Related Keywords:

  • Lung Cancer
  • Non-Small-Cell Lung Cancer
  • resectable
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida  33612