Molecular and Genetic Changes in Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) Following Neoadjuvant Chemotherapy With Cisplatin and Alimta - Phase II Study
18 Years
N/A
Both
Lung Cancer
Trial Information
Molecular and Genetic Changes in Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) Following Neoadjuvant Chemotherapy With Cisplatin and Alimta - Phase II Study
OBJECTIVES:
Primary
- Determine the pathologic complete response in patients with stage IB-IIIB non-small
cell lung cancer treated with neoadjuvant chemotherapy comprising pemetrexed disodium
and cisplatin followed by surgery and adjuvant pemetrexed disodium and cisplatin.
Secondary
- Determine the adverse events of this regimen in these patients.
- Determine the overall and disease-free survival of patients treated with this regimen.
- Correlate response with the presence or absence of ERCC1 and DHFR, thymidylate
synthase, DPD, and GARFT in patients treated with this regimen.
- Correlate the fragile site on chromosome 12 within the SMRT gene with metastasis after
definitive treatment with this regimen in these patients.
OUTLINE:
- Neoadjuvant chemotherapy: Patients receive pemetrexed disodium IV over 10 minutes
followed by cisplatin IV over approximately 1 hour on day 1. Treatment repeats every 21
days for 3 courses. Patients are then evaluated for disease resectability. Patients
with no evidence of disease progression proceed to thoracotomy within the next 28-48
days.
- Thoracotomy: Patients found to have unresectable disease during thoracotomy receive
further treatment off study. Patients with resectable disease undergo complete surgical
resection of the tumor. Forty to eighty days later, patients proceed to adjuvant
chemotherapy.
- Adjuvant chemotherapy: Patients receive pemetrexed disodium and cisplatin as before for
2 courses.
Patients with progressive disease after completion of neoadjuvant chemotherapy are followed
every 6 months. All other patients are followed every 3 months for 2 years, every 6 months
for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study over 6.5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Microscopically confirmed non-small cell lung cancer
- Stage IB (T2, N0, M0), IIA (T1, N1, M0), IIB (T2, N1, M0 or T3, N0, M0), or IIIA
(T1-3, N1-2, M0) disease
- Satellite lesions in one lobe (T4) (stage IIIB) allowed
- Meets 1 of the following criteria:
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 10 mm in
the longest diameter
- Evaluable disease, defined as lesions on chest CT scan that are not measurable
(e.g., ill-defined masses or mediastinal or hilar adenopathy)
- No metastatic disease except peribronchial/hilar lymph nodes (N1) or
ipsilateral/subcarinal mediastinal lymph nodes (N2)
- No N3 lymph nodes (e.g., contralateral mediastinal/hilar or
supraclavicular/scalene) by CT scan or positron emission tomography (PET) scan
AND mediastinoscopy
- No T4 primary tumor (e.g., mediastinal invasion)
- No malignant pleural effusion
- Nonmalignant effusions (i.e., negative cytology, non-bloody, and transudate)
allowed
- Effusions visible only by CT scan and not large enough for safe thoracentesis
allowed
- No exudative effusion, defined by 1 of the following criteria:
- Pleural fluid protein:serum protein ratio > 0.5
- Pleural fluid lactic dehydrogenase (LDH):serum LDH ratio ≥ 0.6
- Pleural fluid LDH > 200 IU/L
- No more than 1 area of fludeoxyglucose (FDG) uptake outside the area of the primary
lung tumor OR evidence of malignant pleural disease as evidenced by pleural nodules
by PET scan
- Single areas of FDG uptake will be further evaluated (e.g., by biopsy) for
metastatic disease
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- WBC ≥ 3,000/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
Hepatic
- Bilirubin ≤ 1.5 mg/dL
- SGOT or SGPT ≤ 1.5 times upper limit of normal
Renal
- Creatinine clearance ≥ 45 mL/min
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment
- No other active malignancy within the past 2 years except nonmelanoma skin cancer or
carcinoma in situ of the cervix
- No psychological, familial, sociological, or geographical situation that would
preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior chemotherapy for lung cancer
Endocrine therapy
- Not specified
Radiotherapy
- No prior radiotherapy for lung cancer
Surgery
- No prior surgery for lung cancer
- At least 12 weeks since prior major surgery to the chest and abdomen
Other
- No concurrent aspirin or other nonsteroidal anti-inflammatory drugs for ≥ 2 days
before (5 days for drugs with a long half-life [e.g., naproxen, piraoxicam,
difunisal, nabumetone, rofecoxib, or celecoxib] or 8 days for long acting agents),
during, and for 2 days after completion of each pemetrexed disodium administration
- No concurrent participation in another study involving chemotherapy or radiotherapy
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathologically complete response
Outcome Time Frame:
1 year
Safety Issue:
No
Principal Investigator
Grace K. Dy, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000441025
NCT ID:
NCT00248495
Start Date:
June 2005
Completion Date:
Related Keywords:
- Lung Cancer
- stage IIIA non-small cell lung cancer
- stage IIIB non-small cell lung cancer
- stage II non-small cell lung cancer
- stage I non-small cell lung cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
