Breast cancer mamma carcinoma
Conditions
Interventions
Patients participating in the imaging arm with an AUC below 550 µg*hr/L at day
14 will be randomized in a 2:1 ratio to undergo dose escalation or not. Dose
escalation will be performed according to
Sponsors
Universitair Medisch Centrum Sint Radboud
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Adult women (* 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy. - Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer - Postmenopausal women - Progression following a non-steroidal aromatase inhibitor - Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrollment. - Falling into one of the following categories: o elderly patients (age * 70 years and BMI
Exclusion criteria
Exclusion criteria: - Patients aged * 70 years AND BMI * 30 kg/m2 - HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive) - Previous treatment with exemestane or mTOR inhibitors. Except for the treatment with exemestane in the adjuvant setting - Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin) - Patients with a known history of HIV seropositivity - Any severe and / or uncontrolled medical condition such as: o Unstable angina pectoris, serious uncontrolled cardiac arrhythmia o Patients with severe hepatic impairment (Child-Pugh A/B/C) o Uncontrolled diabetes mellitus o Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome) - Patients who test positive for hepatitis B or C (Patients who test negative for HBV-DNA, HBsAg, and HBcAb but positive for HBsAb with prior history of vaccination against Hepatitis B will be eligible). Only patients at higher risk for hepatitis B or C have to be tested. - Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days prior to enrollment - History of non-compliance to medical regimens or patients unwilling to or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary aim is to show a difference in everolimus exposure (AUC0-24hr) of at least 25% in elderly patients (*70 years) and obese patients (BMI * 30 kg/m2) compared to the control group ( * 70 years ; BMI * 30 kg/m2), after reaching steady state everolimus pharmacokinetics (day 14, but at least after 7 days of everolimus therapy). | — |
Secondary
| Measure | Time frame |
|---|---|
| - To explore and calculate the correlation of early metabolic response assessment with progression free survival (PFS; defined as disease progression according to RECIST version 1.1 or death, whichever occurs first) as primary outcome measure. - To explore, quantify and describe the correlation between early metabolic response and everolimus exposure (AUC0-24hr), on steady-state pharmacokinetics. - To explore, quantify and describe whether dose escalation in patients who are hypothetically underexposed will result in an increase in metabolic response. - To explore, quantify and describe the correlation between everolimus exposure and the frequency of adverse events as graded with CTCAE v4.0. | — |
Countries
Netherlands
Outcome results
None listed