A Phase 2 Study of Neratinib and Neratinib Plus Temsirolimus in Patients with Non-Small Cell Lung Cancer Carrying Known HER2 Activating Mutations.
Primary objective is to determine progression free survival following treatment with Neratinib and Neratinib plus Temsirolimus in patients with non-small cell lung cancer carrying known HER2 activating mutations who have received at least one prior treatment of chemotherapy. Changes in HER2 mutation in tumor specimens and in circulating plasma DNA will also be explored
Confirmed stage IV non-small cell lung cancer. Documented ErbB2 (HER2) activating mutation. Progressive disease after at least one prior cytotoxic chemotherapy regimen. Normal blood and organ functions. LVEF greater than 50%. No symptomatic or unstable brain metastases; chronic gastrointestinal disorder with diarrhea as major symptom; unstable diabetes with HbA1c greater than 6.5% ; uncontrolled cardiac disease; treatment with investigational agent or surgery less than 28 days prior to initiation of treatment. No prior treatment with TKI or mTOR inhibitor.
Patients will be randomized to one of two arms:â?? ARM A: Neratinib 240 mg orally once dailyâ?? ARM B: Neratinib 240 mg orally once daily plus Temsirolimus 8 mg once weekly by IV infusion.In the case of disease progression on ARM A patients may be given option to add Temsirolimus 8 mg once weekly by IV infusion.Patients on ARM B may be dose-escalated to Temsirolimus 15mg/week after first cycle (21 days), if well tolerated at physicianâ??s discretion. If unacceptable toxicity develops, patients will be dose reduced back to Temsirolimus 8 mg/week dosing.Dosing will be continuous on 3-week cycles until evidence of progressive disease or unacceptable toxicity.
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