Breast NeoplasmsPhase 4INPRESNCT01948960
Influence of Exceptional Patient Characteristics on Everolimus Exposure
A Phase 4 study testing everolimus dose escalation in people with Breast Neoplasms, run by Radboud University Medical Center at 7 sites in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- everolimus dose escalation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 7 sitesNetherlands
- Study dates
- Aug 2013to 15 Jan 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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:
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- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Netherlands7 sites
Maasziekenhuis Pantein
Boxmeer
Spaarne Gasthuis
Hoofddorp
Maastricht University Medical Center
Maastricht
St. Antonius Ziekenhuis
Nieuwegein
Radboud university medical center
Nijmegen
Bernhoven Ziekenhuis
Uden
Isala Klinieken
Zwolle
About this study
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
- Breast Neoplasms
- Being tested
- everolimus dose escalation
- Keywords
- Breast Neoplasms, everolimus, pharmacokinetics, elderly patients, obese patients
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimus dose escalationDrug
patients with an AUC below mean will have dose escalation of everolimus based on their AUC
| Study group | Role | What they receive |
|---|---|---|
| standard care | No intervention | everolimus dose is continued independently of everolimus AUC |
| everolimus dose escalation | Active comparator | patients with an AUC below mean will have dose escalation of everolimus based on their AUC Receives: Drug: everolimus dose escalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
everolimus AUC
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).
Measured: day 14 after start treatment
Secondary outcomes (4)
correlation between early metabolic response and PFS
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.
Measured: within 90 days after start of treatment
correlation between early metabolic response and AUC
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.
Measured: 15 days after start of treatment
effect dose escalation on metabolic respons
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.
Measured: within 36 days after start of treatment
correlation between AUC and frequency of adverse event
To explore, quantify and describe the correlation between everolimus exposure and the frequency of adverse events as graded with CTCAE v4.0.
Measured: 4 months after start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2013 (estimated)
- Study startAug 2013
- Primary completion15 Jan 2018
- Study completion15 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Carla van Herpen, MD, PhD, Principal investigator, Radboud university medical center, department of medical oncologyNielka van Erp, PharmD, PhD, Principal investigator, Radboud university medical center, department of Pharmacy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01948960
- Sponsor's protocol ID
- UMCNONCO201301
- Acronym
- INPRES
- Status last verified
- Oct 2017
- First submitted
- 13 Sep 2013
- Last updated
- 7 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30259313
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Exceptional Patient Characteristics on Everolimus Exposure
- ClinicalTrials.gov ID
- NCT01948960
- Acronym / sponsor ID
- INPRES / UMCNONCO201301
- Conditions
- Breast Neoplasms
- Keywords
- Breast Neoplasms, everolimus, pharmacokinetics, elderly patients, obese patients
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Aug 2013
- Primary completion
- 15 Jan 2018 (actual)
- Study completion
- 15 Jan 2018 (actual)
- First posted
- 24 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| standard care | No intervention | –everolimus dose is continued independently of everolimus AUC |
| everolimus dose escalation | Active comparator | Drug: everolimus dose escalationpatients with an AUC below mean will have dose escalation of everolimus based on their AUC |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimus dose escalationpatients with an AUC below mean will have dose escalation of everolimus based on their AUC | Drug | everolimus dose escalation |
Primary outcome
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).
4 secondary outcomes
correlation between early metabolic response and PFS
Time frame: within 90 days after start of treatment
correlation between early metabolic response and AUC
Time frame: 15 days after start of treatment
effect dose escalation on metabolic respons
Time frame: within 36 days after start of treatment
correlation between AUC and frequency of adverse event
Time frame: 4 months after start of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2018.
- Derived from this study: PubMed 30259313Willemsen 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.
- Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and ExemestaneLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carla van Herpen, MD, PhD principal investigator
Radboud university medical center, department of medical oncology
Nielka van Erp, PharmD, PhD principal investigator
Radboud university medical center, department of Pharmacy
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing everolimus dose escalation in people with Breast Neoplasms, run by Radboud University Medical Center at 7 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
everolimus AUC (time frame: day 14 after start treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01948960, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2018.