Influence of Exceptional Patient Characteristics on Everolimus Exposure (INPRES)

December 5, 2018 updated by: Radboud University Medical Center

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
56

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Boxmeer, Netherlands
        • Maasziekenhuis Pantein
      • Hoofddorp, Netherlands
        • Spaarne Gasthuis
      • Maastricht, Netherlands
        • Maastricht University Medical Center
      • Nieuwegein, Netherlands
        • St. Antonius Ziekenhuis
      • Nijmegen, Netherlands
        • Radboud University Medical Center
      • Uden, Netherlands
        • Bernhoven Ziekenhuis
      • Zwolle, Netherlands
        • Isala Klinieken

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: standard care
everolimus dose is continued independently of everolimus AUC
Active Comparator: everolimus dose escalation
patients with an AUC below mean will have dose escalation of everolimus based on their AUC
Drug: everolimus dose escalation
patients with an AUC below mean will have dose escalation of everolimus based on their AUC

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
everolimus AUC
Time Frame: day 14 after start treatment
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).
day 14 after start treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
correlation between early metabolic response and PFS
Time Frame: within 90 days after start of treatment

To explore and calculate the predictive value of early metabolic response assessment with clinical benefit (PFS defined as disease progression according to RECIST version 1.1 or death, whichever occurs first) as primary outcome measure.

Metabolic response is defined as fractional change (ΔSUV and ΔTLG), comparing the third en second scan with the baseline scan.
within 90 days after start of treatment
correlation between early metabolic response and AUC
Time Frame: 15 days after start of treatment

To quantify the correlation between early metabolic response and everolimus exposure (AUC0-24hr) on steady-state pharmacokinetics.

Metabolic response is defined as fractional change (ΔSUV and ΔTLG), comparing the third en second scan with the baseline scan.
15 days after start of treatment
effect dose escalation on metabolic respons
Time Frame: within 36 days after start of treatment

To explore, quantify and describe whether dose escalation in patients who are hypothetically underexposed will result in an increase in metabolic response.

Metabolic response is defined as fractional change (ΔSUV and ΔTLG), comparing the third en second scan with the baseline scan.
within 36 days after start of treatment
correlation between AUC and frequency of adverse event
Time Frame: 4 months after start of treatment
To explore, quantify and describe the correlation between everolimus exposure and the frequency of adverse events as graded with CTCAE v4.0.
4 months after start of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Radboud University Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novartis

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Carla van Herpen, MD, PhD, Radboud university medical center, department of medical oncology
  • Principal Investigator: Nielka van Erp, PharmD, PhD, Radboud university medical center, department of Pharmacy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 15, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 15, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 13, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 19, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 24, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 7, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UMCNONCO201301

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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