Influence of Exceptional Patient Characteristics on Everolimus Exposure (INPRES)

Radboud University Medical Center

Status and phase: Completed; Phase 4

Conditions: Breast Neoplasms

Treatments: Drug: everolimus dose escalation

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01948960

UMCNONCO201301

Details and patient eligibility

About

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.

Enrollment: 56 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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56 participants in 2 patient groups

standard care

No Intervention group

Description:

everolimus dose is continued independently of everolimus AUC

everolimus dose escalation

Active Comparator group

Description:

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

Treatment:

Drug: everolimus dose escalation