A Phase I/II Trial of an Oral MTOR Protein Kinase Inhibitor (Everolimus, RAD001) in Combination With an Oral EGFR Tyrosine Kinase Inhibitor (Erlotinib, Tarceva™) In Patients With Metastatic Breast Cancer
- 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).
- 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
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
at 4 weeks
Ingrid Mayer, MD
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
VICC BRE 0523
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Vanderbilt-Ingram Cancer Center - Cool Springs||Nashville, Tennessee 37064|
|Vanderbilt-Ingram Cancer Center at Franklin||Nashville, Tennessee 37064|