Erlotinib and Everolimus in Treating Patients With Metastatic Breast Cancer
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.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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 maximum tolerated dose (MTD) of RAD001 given in combination with erlotinib (Phase I) [ Time Frame: at 4 weeks ] [ Designated as safety issue: Yes ]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.
- Anti-tumor activity of RAD001 in combination with erlotinib (Phase II) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]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 to progression (Phase II) [ Time Frame: from study entry to disease progression ] [ Designated as safety issue: No ]Duration of time to progression of disease.
- To determine PTEN, pAkt, pP70S6K1 and pEGFR in primary tumors at baseline. [ Time Frame: at day one ] [ Designated as safety issue: No ]Breast tissue paraffin-embedded blocks from patients's pre-treatment diagnostic surgery
|Study Start Date:||December 2005|
|Study Completion Date:||February 2009|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
Experimental: Erlotinib/RAD001 Ph I
Tarceva (OSI-774; erlotinib) Everolimus (RAD001)
Study did not progress to Phase II:
Experimental: Erlotinib/RAD001 Phase II Maximum tolerated dose of erlotinib (Tarceva,OSI-774) and RAD001 (Everolimus)
Other Name: Tarceva (OSI-774)Drug: RAD001
minus 1: RAD001 2.5 mg/d
minus 2: RAD001 2.5 every other day
Other Name: everolimus
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00574366
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|Vanderbilt-Ingram Cancer Center - Cool Springs|
|Nashville, Tennessee, United States, 37064|
|Vanderbilt-Ingram Cancer Center at Franklin|
|Nashville, Tennessee, United States, 37064|
|Study Chair:||Ingrid Mayer, MD||Vanderbilt-Ingram Cancer Center|