Genetic Changes in Patients With Non-Small Cell Lung Cancer Who Are Receiving Vinorelbine and Gemcitabine Before Surgery
Molecular And Genetic Changes In Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) Following Neoadjuvant Chemotherapy With Vinorelbine And Gemcitabine - Phase II Study
RATIONALE: Determination of genetic changes in patients with non-small cell lung cancer may help predict the outcome of treatment. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them before surgery, may shrink the tumor so that it can be removed during surgery.
PURPOSE: Phase II trial to study genetic changes and the effectiveness of combining vinorelbine with gemcitabine before surgery in treating patients who have stage IB, stage II, or stage III non-small cell lung cancer.
Studieoversikt
Status
Status
Forhold
Forhold
Intervensjon / Behandling
Intervensjon / Behandling
Detaljert beskrivelse
OBJECTIVES:
- Determine the frequency of expression of epithelial markers CK19, CK20, MUC1, and MUC5 (by reverse transcriptase-polymerase chain reaction) in lymph node tissue and blood samples of patients with resectable stage IB-III non-small cell lung cancer treated with neoadjuvant vinorelbine and gemcitabine followed by surgery.
- Determine the expression of the multidrug resistance-associated protein gene before and after treatment with this regimen in these patients.
- Determine the global expression profile of genes (by microarray technology) in tumor tissue of patients treated with this regimen.
- Determine the frequency of loss of heterozygosity at several loci on chromosomes 3p, 9p, and 11p before and after treatment with this regimen in these patients.
- Determine the percent positivity of cells that stain for MCM2 and CDC6 (prereplicative complex) by immunohistochemistry before and after treatment with this regimen in these patients.
- Determine the feasibility of this regimen in these patients.
- Determine the pathological response rates in patients treated with this regimen.
- Determine the side effects of this regimen in these patients.
- Determine the disease-free and overall survival of patients treated with this regimen.
- Determine the autologous immune response in patients treated with this regimen.
OUTLINE: Patients receive vinorelbine IV over 6-10 minutes and gemcitabine IV over 30 minutes on days 1, 8, 22, and 29 in the absence of disease progression or unacceptable toxicity.
Patients with no disease progression by scans or bronchoscopy undergo surgical resection between days 57-70 (weeks 8-10).
Loss of heterozygosity (LOH) at loci on chromosomes 3p, 9p, and 11p is assessed in blood specimens, tumor tissue, and noncancerous tissue before and after chemotherapy. Specimens are also examined for molecular markers of occult metastasis using reverse transcriptase-polymerase chain reaction. Multidrug resistance-associated protein gene expression is also determined using microarray technology.
Patients are followed every 3 months for 2 years, every 6 months for 5 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2 years.
Studietype
Studietype
Registrering (Faktiske)
Registrering
Fase
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
-
-
New York
-
Buffalo, New York, Forente stater, 14263-0001
- Roswell Park Cancer Institute
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
DISEASE CHARACTERISTICS:
Histologically confirmed non-small cell carcinoma of the lung
- May be confirmed at the initial bronchoscopy and mediastinoscopy
- Stage IB (T2, N0, M0)
- Stage IIA (T1, N1, M0)
- Stage IIB (T2-3, N0-1, M0)
- Stage IIIA (T1-3, N1-2, M0)
- stage IIIB (2 lesions in 1 lobe [T4])
- No N3 lymph nodes (contralateral mediastinal/hilar and supraclavicular/scaline) OR T4 primary tumor (malignant pleural effusion or mediastinal invasion) by clinical staging criteria (seen on CT or PET scan and proven by mediastinoscopy)
No metastatic disease (except N1 or N2 disease) or malignant pleural effusion* detected on preoperative evaluation
No exudative effusions (even if cytologically negative)
Pleural fluid is considered exudative if the following apply:
- Ratio of pleural fluid protein to serum protein is greater than 0.5
- Ratio of pleural fluid lactic dehydrogenase (LDH) to serum LDH is at least 0.6
- Pleural fluid LDH is greater than 200 IU/L
- No multiple areas of fluorodeoxyglucose (FDG) uptake** outside the area of the primary tumor in the lung NOTE: *Effusions visible only on CT scan and not large enough for safe thoracentesis are allowed
NOTE: **If only 1 area shows an increase in FDG uptake, the area of concern requires further evaluation (e.g., biopsy) to exclude metastatic disease
- Bidimensionally measurable or evaluable disease* NOTE: *Lesions apparent on chest CT scan (e.g., ill-defined masses associated with post obstructive changes and mediastinal or hilar adenopathy measurable in 1 dimension) are considered evaluable
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Not specified
Life expectancy
- Not specified
Hematopoietic
- WBC at least 3,000/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 9 g/dL
Hepatic
- Bilirubin no greater than 1.5 mg/dL
- AST or ALT no greater than 1.5 times upper limit of normal
Renal
- Creatinine no greater than 1.5 mg/dL
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Deemed medically fit for surgical resection
- No other active malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- No psychological, sociological, or geographical condition that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Concurrent participation in the RPCI vaccine study (postoperative vaccination with autologous tumor-associated antigen-pulsed dendritic cells) is allowed
Chemotherapy
- No prior chemotherapy for lung cancer
- No concurrent participation in another study involving other chemotherapy agents
Endocrine therapy
- Not specified
Radiotherapy
- No prior radiotherapy for lung cancer
- No concurrent participation in another study involving radiotherapy
Surgery
- No prior surgery for lung cancer
- More than 3 months since other prior major surgery (e.g., coronary artery bypass graft)
Other
- No other prior therapy for lung cancer
- No other concurrent antineoplastic agents
- Concurrent participation in observational studies requiring bloodwork, radiographs, pulmonary function tests, or quality of life studies is allowed
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
Samarbeidspartnere og etterforskere
Sponsor
Sponsor
Etterforskere
Etterforskere
- Studiestol: Nithya Ramnath, MD, Roswell Park Cancer Institute
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Ramnath N, Sommers E, Anderson T, et al.: Neoadjuvant gemcitabine and vinorelbine in non-small-cell lung cancer (NSCLC). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2818, 2003.
Studierekorddatoer
Studer hoveddatoer
Studiestart
Studiestart
Primær fullføring (Faktiske)
Primær fullføring
Studiet fullført (Faktiske)
Studiet fullført
Datoer for studieregistrering
Først innsendt
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Først lagt ut
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Sist oppdatering lagt ut
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Sykdommer i luftveiene
- Neoplasmer
- Lungesykdommer
- Neoplasmer etter nettsted
- Neoplasmer i luftveiene
- Thoracale neoplasmer
- Karsinom, bronkogent
- Bronkiale neoplasmer
- Lungeneoplasmer
- Karsinom, ikke-småcellet lunge
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Antivirale midler
- Enzymhemmere
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Tubulin modulatorer
- Antimitotiske midler
- Mitosemodulatorer
- Antineoplastiske midler, fytogene
- Gemcitabin
- Vinorelbin
Andre studie-ID-numre
Andre studie-ID-numre
- CDR0000270753
- RPCI-RP-00-01
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