Influence of Exceptional Patient Characteristics on Everolimus Exposure
Information source: Radboud University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Breast Neoplasms
Intervention: everolimus dose escalation (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Radboud University Official(s) and/or principal investigator(s): Carla van Herpen, MD, PhD, Principal Investigator, Affiliation: Radboud university medical center, department of medical oncology Nielka van Erp, PharmD, PhD, Principal Investigator, Affiliation: Radboud university medical center, department of Pharmacy
Overall contact: Carla van Herpen, MD, PhD, Email: Carla.vanHerpen@radboudumc.nl
Summary
A study to determine whether everolimus pharmacokinetics in elderly and obese patients is
different compared to control patients.
Furthermore the investigators will investigate the relation between metabolic response
assessed with [18F] Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) and everolimus
exposure and clinical benefit.
The investigators will explore whether dose escalation in patients who are hypothetically
underexposed will result in an increase in metabolic response.
Clinical Details
Official title: Influence of Exceptional Patient Characteristics on Everolimus Exposure
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Primary outcome: everolimus AUC
Secondary outcome: correlation between early metabolic response and PFScorrelation between early metabolic response and AUC effect dose escalation on metabolic respons
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
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
- Radiological or clinical evidence of recurrence or progression on last systemic
therapy prior to enrollment.
- Progression following a non-steroidal aromatase inhibitor
- Falling into one of the following categories
- elderly patients (age ≥ 70 years and BMI < 30 kg/m2); or
- obese patients (BMI ≥ 30 kg/m2 and age < 70 years); or
- 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 ≥ 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 conditions such as:
- Unstable angina pectoris, serious uncontrolled cardiac arrhythmia
- Patients with severe hepatic impairment (Child-Pugh A/B/C)
- Uncontrolled diabetes mellitus
- 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 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
- Patients unwilling to or unable to comply with the protocol
Locations and Contacts
Carla van Herpen, MD, PhD, Email: Carla.vanHerpen@radboudumc.nl
Maasziekenhuis Pantein, Boxmeer, Netherlands; Recruiting Yvonne Kamm, MD, PhD
Maastricht University Medical Center, Maastricht, Netherlands; Recruiting Maaike de Boer, MD, PhD, Principal Investigator
St. Antonius Ziekenhuis, Nieuwegein, Netherlands; Recruiting Paul de Jong, MD, PhD
Radboud university medical center, Nijmegen, Netherlands; Recruiting Annelieke Willemsen, MD, Email: annelieke.willemsen@radboudumc.nl Carla van Herpen, MD, PhD, Principal Investigator
Bernhoven Ziekenhuis, Uden, Netherlands; Recruiting Allert Vos, MD, Principal Investigator
Isala Klinieken, Zwolle, Netherlands; Recruiting Jan Willem de Groot, MD, PhD
Additional Information
Starting date: August 2013
Last updated: May 8, 2015
|