Influence of Exceptional Patient Characteristics on Everolimus Exposure

NCT ID: NCT01948960

Last Updated: 2018-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-08-31

Study Completion Date

2018-01-15

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Neoplasms

Keywords

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Breast Neoplasms everolimus pharmacokinetics elderly patients obese patients

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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standard care

everolimus dose is continued independently of everolimus AUC

Group Type NO_INTERVENTION

No interventions assigned to this group

everolimus dose escalation

patients with an AUC below mean will have dose escalation of everolimus based on their AUC

Group Type ACTIVE_COMPARATOR

everolimus dose escalation

Intervention Type DRUG

patients with an AUC below mean will have dose escalation of everolimus based on their AUC

Interventions

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everolimus dose escalation

patients with an AUC below mean will have dose escalation of everolimus based on their AUC

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Carla van Herpen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud university medical center, department of medical oncology

Nielka van Erp, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud university medical center, department of Pharmacy

Locations

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Maasziekenhuis Pantein

Boxmeer, , Netherlands

Site Status

Spaarne Gasthuis

Hoofddorp, , Netherlands

Site Status

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status

St. Antonius Ziekenhuis

Nieuwegein, , Netherlands

Site Status

Radboud university medical center

Nijmegen, , Netherlands

Site Status

Bernhoven Ziekenhuis

Uden, , Netherlands

Site Status

Isala Klinieken

Zwolle, , Netherlands

Site Status

Countries

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Netherlands

References

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Willemsen 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.

Reference Type DERIVED
PMID: 30259313 (View on PubMed)

Related Links

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https://www.ncbi.nlm.nih.gov/pubmed/30259313

Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane

Other Identifiers

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UMCNONCO201301

Identifier Type: -

Identifier Source: org_study_id