RATIONALE: Erlotinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib together with everolimus may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of giving erlotinib together with everolimus and to see how well it works in treating patients with metastatic breast cancer.
OBJECTIVES: Primary * To determine the safety of everolimus given in combination with erlotinib hydrochloride in patients with metastatic breast cancer (phase I). * To determine the antitumor activity of the combination (phase II). * Determine the rate of clinical benefit (complete response + partial response + stable disease for at least 6 months) in patients with metastatic breast cancer (phase II). Secondary * To determine the time to progression. * To determine PTEN, pAkt, pP70S6K1 and pEGFR in primary tumors at baseline. OUTLINE: This is an open-label, dose escalation phase I study followed by an open-label phase II study. * Phase I: Patients receive escalating doses of oral everolimus and oral erlotinib hydrochloride once daily until the maximum tolerated dose (MTD) is determined. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Once the MTD is reached, the recommended dose to be used in the phase II portion of the study is identified. * Phase II: Patients receive oral everolimus and oral erlotinib hydrochloride as in phase I at the recommended phase II dose determined in phase I. Patients undergo tissue collection to evaluate tumor levels of PTEN, pAkt, pP70S6K1, and pEGFR at baseline in order to identify predictors of therapeutic response. After completion of study treatment, patients are followed every 3 months for 2 years (from study entry), every 6 months for 3 years, and annually thereafter. NOTE: Phase I completed. Investigator did not proceed with Phase II
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Levels: * 1 Erlotinib 50 mg/d * 2 Erlotinib 50 mg/d * 1 Erlotinib 100 mg/d * 2 Erlotinib 100 mg/d * 3 Erlotinib 150 mg/d * 4 Erlotinib 150 mg/d
Levels minus 1: RAD001 2.5 mg/d minus 2: RAD001 2.5 every other day 1. RAD001 2.5 mg per day 2. RAD001 5 mg per day 3. RAD001 10 mg per day 4. RAD001 10 mg per day
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
To determine the maximum tolerated dose (MTD) of RAD001 given in combination with erlotinib (Phase I)
MTD will be the dose level at which fewer than 2 of 6 (or 33% of) patients experience dose limiting toxicity (DLT), starting at first 4 weeks.
Time frame: at 4 weeks
Anti-tumor activity of RAD001 in combination with erlotinib (Phase II)
Clinical benefit based upon number of patients with complete response (CR), partial response (PR), and stable disease (SD). Responses are determined by Response Evaluation in Solid Tumors (RECIST)criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in the sum of the longest diameter (LD) of target lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
Time frame: at 6 months
Time to progression (Phase II)
Duration of time to progression of disease.
Time frame: from study entry to disease progression
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