Combination Treatment With Everolimus, Letrozole and Trastuzumab in Hormone Receptor and HER2/Neu-Positive Patients With Advanced Metastatic Breast Cancer and Other Solid Tumors: Evaluating Synergy and Overcoming Resistance
This phase I trial studies the side effects and best dose of everolimus and trastuzumab when given together with letrozole in treating patients with hormone receptor-positive and human epidermal growth factor (EGF) receptor 2 (HER2)-positive breast cancer or other solid tumors that have spread to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by tumor cells. Immunotherapy with monoclonal antibodies, such as trastuzumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving everolimus, letrozole, and trastuzumab together may be a better treatment for breast cancer and other solid tumors than everolimus alone.
• Signed informed consent obtained prior to any screening procedures
• Performance status =\< 1
• Absolute neutrophil count (ANC) \>= 1 x 10\^9/L
• Platelets \>= 75 x 10\^9/L
• Hemoglobin (Hb) \> 8 g/dL
• Total serum bilirubin =\< 2.0 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN) (=\< 5 x ULN in patients with liver metastases)
• International normalized ratio (INR) =\< 2
• Serum creatinine =\< 1.5 x ULN
• Fasting serum cholesterol =\< 300 mg/dL or =\< 7.75 mmol/L and fasting triglycerides =\< 2.5 x ULN; Note: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
• Histologically confirmed advanced solid tumors with HR-positivity defined as \> 1% on immunohistochemistry (estrogen receptor-positive with or without positivity for the progesterone receptor) and HER2/neu positivity (3+ on IHC and/or 2+ on IHC and FISH amplified, or by v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 \[ERBB2\] mutation on next generation sequencing)
• Must have measurable or evaluable disease
• At least 4 weeks since the last dose of chemotherapy, immunotherapy, surgery, or radiation therapy (exception: patients may have received palliative low dose radiation therapy one week before treatment provided it is not given to the only targeted lesions); at least 6 weeks for therapy which is known to have delayed toxicity (nitrosoureas, mitomycin-C, and liposomal doxorubicin); at least 4 weeks (or 5 half-lives, whichever is shorter) since treatment with biologic/targeted therapies; at least 2 weeks since last hormonal therapy
• Female patients must either be: post-menopausal women as defined by a) age \>= 60 years of age; b) prior bilateral oophorectomy; c) age \< 60 with at least 12 months of spontaneous amenorrhea or post-menopausal range follicle stimulating hormone (FSH) and estradiol levels or premenopausal women receiving a gonadotropin-releasing hormone agonist
• Patient may have had any number of prior chemotherapy regimens in the adjuvant/neoadjuvant and/or metastatic setting (including none)
• Patient may have had any number of prior treatments with anti-HER2 strategies in the adjuvant/neoadjuvant and/or metastatic setting (including none)
• Patient may have had any number of prior hormonal therapies in the adjuvant/neoadjuvant and/or metastatic setting (including none)
• Breast cancer patients in the expansion cohort must be hormone sensitive or have refractory disease