A Randomized Phase II Study of Gemcitabine and Carboplatin With or Without MK-0646 as First-Line Therapy in Advanced Squamous Non-Small Cell Lung Carcinoma
- To assess and compare the progression-free survival of patients with stage IIIB or IV
squamous cell non-small cell lung cancer treated with gemcitabine hydrochloride and
carboplatin with vs without MK-0646 as first-line therapy.
- To assess and compare the objective tumor response rate in patients treated with these
- To assess and compare the duration of response in patients with objective tumor
response treated with these regimens.
- To assess and compare the time to progression and time to treatment failure in patients
treated with these regimens.
- To assess and compare the 1-year overall survival of patients treated with these
- To assess and compare the clinical toxicities of these regimens in these patients.
- To compare the quality of life of patients treated with these regimens.
- To collect blood and tumor specimens for future evaluation of pharmacogenetic and
proteomic markers of tumor response and toxicity to therapy.
- To assess the relationship between ht-SNPs in genes that mediate
chemosensitivity/resistance to gemcitabine hydrochloride (e.g. ribonucleotide
reductase) and IGF1R pathway genes.
- To bank paraffin-embedded tissue blocks/slides for future histochemistry evaluation and
DNA extraction as part of ongoing research for NCCTG lung studies.
OUTLINE: This is a multicenter study. Patients are stratified according to prior adjuvant
therapy, neoadjuvant therapy, or chemoradiotherapy (yes vs no), and ECOG performance status
(0 vs 1 vs 2). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8,
carboplatin IV over 30 minutes on day 1, and MK-0646 IV over 60 minutes on days 1, 8,
and 15. Treatment repeats every 21 days for 4 courses in the absence of disease
progression or unacceptable toxicity. After 4 courses, patients with stable disease or
partial or complete response may then receive MK-0646 alone on days 1 and 15. Treatment
with MK-0646 repeats every 28 days in the absence of disease progression or
- Arm II: Patients receive gemcitabine hydrochloride and carboplatin as in arm I.
Treatment repeats every 21 days for 4 courses in the absence of disease progression or
unacceptable toxicity. Patients may crossover to arm I upon disease progression.
Blood and tissue samples may be collected for pharmacogenetics and further laboratory
Quality of life is assessed at baseline and periodically during study.
After completion of study treatment, patients are followed up periodically for up to 5
Allocation: Randomized, Primary Purpose: Treatment
Grace K. Dy, MD
Roswell Park Cancer Institute