Influence of exceptional patient characteristics on everolimus exposure

Phase 4

Completed

Conditions: Breast cancer
mamma carcinoma
10006291

Registration Number: NL-OMON38713

Lead Sponsor: niversitair Medisch Centrum Sint Radboud

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 75

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 < 30 kg/m2); or
o obese patients (BMI * 30 kg/m2 and age < 70 years); or
o control patients (BMI < 30 kg/m2 and age < 70 years);
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) * 5 x ULN
- Adequate renal function: calculated creatinine clearance (as estimated by GFR using the MDRD formula) is MDRD * 30ml/min/1.73m2
- Performance status ECOG 0 - 2 (Karnofsky index: 60 - 100)
- Patient is willing and able to sign the Informed Consent Form prior to screening evaluations

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary aim is to show a difference in everolimus exposure (AUC0-24hr) of<br /><br>at least 25% in elderly patients (70 years) and obese patients (BMI 30<br /><br>kg/m2) compared to the control group ( * 70 years ; BMI * 30 kg/m2), after<br /><br>reaching steady state everolimus pharmacokinetics (day 14, but at least after 7<br /><br>days of everolimus therapy).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- To explore and calculate the correlation of early metabolic response<br /><br>assessment with progression free survival (PFS; defined as disease progression<br /><br>according to RECIST version 1.1 or death, whichever occurs first) as primary<br /><br>outcome measure.<br /><br>- To explore, quantify and describe the correlation between early metabolic<br /><br>response and everolimus exposure (AUC0-24hr), on steady-state pharmacokinetics.<br /><br>- To explore, quantify and describe whether dose escalation in patients who are<br /><br>hypothetically underexposed will result in an increase in metabolic response.<br /><br>- To explore, quantify and describe the correlation between everolimus exposure<br /><br>and the frequency of adverse events as graded with CTCAE v4.0.</p><br>