Clinical trial · Interventional
Influence of Exceptional Patient Characteristics on Everolimus Exposure
NCT01948960CI-TRIAL-00036049INPREScompletedPhase 4ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Neoplasms | Breast Neoplasm | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| everolimus dose escalation | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- NO_INTERVENTION
- label
- standard care
- description
- everolimus dose is continued independently of everolimus AUC
- type
- ACTIVE_COMPARATOR
- label
- everolimus dose escalation
- description
- patients with an AUC below mean will have dose escalation of everolimus based on their AUC
- interventionNames
- Drug: everolimus dose escalation
Primary outcomes (1)
- measure
- everolimus AUC
- timeFrame
- day 14 after start treatment
- description
- 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).
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (1)
- DERIVEDWillemsen AECAB, de Geus-Oei LF, de Boer M, Tol J, Kamm Y, de Jong PC, Jonker MA, Vos AH, Grootjans W, de Groot JWB, Mulder SF, Aarntzen EHJG, Gerritsen WR, van Herpen CML, van Erp NP. Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane. Target Oncol. 2018 Oct;13(5):641-648. doi: 10.1007/s11523-018-0596-8. PMID 30259313