This study will compare the rate of chemotherapy: pemetrexed and cisplatin compared with the combination of pemetrexed/cisplatin with MK-0646. The other purposes are to determine how long we can control the cancer growth and toxicity and safety of the combination. Laboratory research with the tumor tissue and blood obtained will be done to assess IGF-1R expression and related markers and correlate with response and survival.
Insulin-like Growth factor 1 receptor (IGF-1R) is a tyrosine kinase receptor that regulates cell growth, proliferation and apoptosis.(4) Increased IGF1 signaling results in upregulation of proliferation and inhibition of apoptosis through RAF and PI3K pathways.(5) Several types of cancer, including non-small cell lung cancer, express IGF-1R and its ligand. The sequestration of IGF by IGF binding protein was associated with improved survival in patients with resected stage I lung cancer.(6) High expression of IGF-1R is associated with poor survival in surgically resected stage I lung cancer, specifically adenocarcinoma subtype. Patients with adenocarcinoma and never smoker had higher expression of IGF-1R vs. squamous cell carcinoma and smokers.(7). Low IGF-1R expression was associated with significant improvement in survival in the adenocarcinoma lung cancer but there was a lack of correlation between expression of IGF1R and survival in patients with squamous cell histology. Monoclonal antibodies target the extracellular domain of IGF-IR and small molecules inhibit IGF-1R kinase. This is a potential new strategy in the treatment of lung cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Pemetrexed: 500mg/m2 IV on day 1 and Cisplatin: 75 mg/m2 IV on day 1 every 21 days x 6 cycles.
Pemetrexed 500 mg/m2 IV on Day 1 and Cisplatin 75 mg/m2 IV on Day 1 every 21 days for 6 cycles in combination with MK-0646 will be given IV, 10 mg/KG, Days 1, 8 and 15 weekly.
Hutchinson Clinic, PA
Hutchinson, Kansas, United States
Kansas University Cancer Center
Kansas City, Kansas, United States
Stormont Vail Healthcare
Topeka, Kansas, United States
VA Medical Center
Kansas City, Missouri, United States
Compare response rate between the two arms.
Time frame: 31 months
Progression-free survival, overall survival and Toxicity profile
Time frame: 31 months
Exploratory Objectives: Assess biomarkers of Pemetrexed, IGF-1R and immunogenicity of MK-0646.
Time frame: 31 months
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