Clinical trial NCT00226577: Pharmacogenomic & Phase II Study of Gemcitabine and Pemetrexed in Non-Small-Cell Lung Cancer.
Official title: Phase II Study of Neoadjuvant Chemotherapy With Gemcitabine and Pemetrexed in Resectable Non-Small-Cell Lung Cancer (NSCLC) With Pharmacogenomic Correlates.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: Non-Small-Cell Lung Cancer
resectable
NSCLC
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Eli Lilly and Company
First posted: 2005-09-27
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Disease Response - Radiographic
timeFrame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
Secondary outcomes:
measure: Disease Response - Pathologic
timeFrame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
measure: Survival - Disease Free
timeFrame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
measure: Survival - Overall
timeFrame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
measure: Toxicity
timeFrame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center (now at Karmanos Cancer Institute)
name: Gerold Bepler, M.D, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: