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

Sponsors and Collaborators:	H. Lee Moffitt Cancer Center and Research Institute National Cancer Institute (NCI) Eli Lilly and Company
Information provided by:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT00226577

Purpose

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.

Condition	Intervention	Phase
Non-Small-Cell Lung Cancer	Drug: Gemcitabine Drug: Pemetrexed Procedure: Surgery	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Official Title:	Phase II Study of Neoadjuvant Chemotherapy With Gemcitabine and Pemetrexed in Resectable Non-Small-Cell Lung Cancer (NSCLC) With Pharmacogenomic Correlates.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Surgery

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Pemetrexed Pemetrexed disodium

U.S. FDA Resources

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:

correlating molecular and genetic parameters to disease response

Secondary Outcome Measures:

complete pathological response at surgery
disease-free survival
overall survival

Estimated Enrollment:	80
Study Start Date:	February 2004

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00226577

Locations

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

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

National Cancer Institute (NCI)

Eli Lilly and Company

Investigators

Principal Investigator:

Gerold Bepler, Md, PhD

H. Lee Moffitt Cancer Center

More Information

Additional Information:

Moffiitt Cancer Center Clinical Trials website This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	MCC-13726
Study First Received:	September 23, 2005
Last Updated:	December 7, 2006
ClinicalTrials.gov Identifier:	NCT00226577 History of Changes
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Thoracic Neoplasms
Antimetabolites
Anti-Infective Agents
Immunologic Factors
Folate
Folinic Acid
Folic Acid Antagonists
Immunosuppressive Agents
Antiviral Agents
Vitamin B9
Carcinoma

Folic Acid
Pemetrexed
Radiation-Sensitizing Agents
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Non-small Cell Lung Cancer
Gemcitabine
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Thoracic Neoplasms
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Gemcitabine
Respiratory Tract Neoplasms

Neoplasms by Histologic Type
Enzyme Inhibitors
Folic Acid Antagonists
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Carcinoma
Pemetrexed
Neoplasms
Radiation-Sensitizing Agents
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 11, 2009