Influence of Exceptional Patient Characteristics on Everolimus Exposure

NCT01948960 | Completed Phase 4

• 1 other identifier: UMCNONCO201301
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Breast Neoplasms

Keywords

Breast Neoplasms; everolimus; pharmacokinetics; elderly patients; obese patients

Outcome Measures

Primary Outcomes (1)

• 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).

  day 14 after start treatment

Secondary Outcomes (4)

• correlation between early metabolic response and PFS

  within 90 days after start of treatment

• correlation between early metabolic response and AUC

  15 days after start of treatment

• effect dose escalation on metabolic respons

  within 36 days after start of treatment

• correlation between AUC and frequency of adverse event

  4 months after start of treatment

Study Arms (2)

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

Drug: everolimus dose escalation

Interventions

everolimus dose escalation DRUG

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

everolimus dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Novartis: collaborator

Study Sites (7)

Maasziekenhuis Pantein

Boxmeer, Netherlands

Location

Spaarne Gasthuis

Hoofddorp, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

St. Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Radboud university medical center

Nijmegen, Netherlands

Location

Bernhoven Ziekenhuis

Uden, Netherlands

Location

Isala Klinieken

Zwolle, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 30259313 DERIVED

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2013
• First Posted: September 24, 2013
• Study Start: August 1, 2013
• Primary Completion: January 15, 2018
• Study Completion: January 15, 2018
• Last Updated: December 7, 2018

Record last verified: 2017-10

Locations

NL (7)