TheranosticTrials.org

Clinical Trial · NCT02028364

Pet Imaging as a Biomarker in Hormone Refractory postmenopausaL Women

Overview

This is a prospective, single arm trial in which patients with locally advanced or metastatic endocrine receptor positive and HER2 negative breast cancer refractory to non-steroidal aromatase inhibitors (NSAI) will receive Everolimus 10mg orally daily given in conjunction with exemestane 25mg orally daily until disease progression or treatment discontinuation for any other reasons. The main objectives are to evaluate if early metabolic response (MR) using FDG-PET/CT is associated with progression free survival (PFS) and overall survival (OS) in this population. Tumour, metastatic lesions and blood samples will be collected during the treatment period in order to identify biomarkers predicting resistance to study treatment. Results will be correlated with the results of early FDG PET/CT data in order to better characterise the non-responders.

Sponsor

Jules Bordet Institute

Phase

Phase 2

Contacts

Andrea Gombos, MD (PRINCIPAL_INVESTIGATOR)

Patrick Flamen, MD (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT02028364

Drug / Compound

FDG

Isotope(s):
Target(s):
  • Glucose Transport
Ligand Class: Small Molecules

Eligibility

Inclusion

  • Platelets ≥100,000/mm3 (≥100x 109/L)
  • Progression while on, or within one month of end of anastrozole or letrozole or treatment for locally advanced or metastatic breast cancer. NOTE: Letrozole or anastrozole do not have to be the last treatment prior to enrolment.
  • The target lesion can be a bone metastasis if it fulfils the above mentioned criteria.
  • FDG-PET measurable disease defined as: at least one target lesion fulfilling following criteria:
  • Adequate liver function as shown by:
  • Breast cancer that is refractory to non-steroidal aromatase inhibitors (NSAI) (i.e. anastrozole or letrozole) defined as:
  • Fasting triglycerides ≤2.5 x ULN
  • Fasting glucose \< 1.5 x ULN
  • In the case the target lesion is a lymph node, the small axis should be ≥ 1.5cm.
  • Total serum bilirubin ≤1.5 x ULN (≤3 ULN for patients known to have Gilbert Syndrome)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5xULN (or ≤5 if hepatic metastases are present)
  • For patients with accessible metastatic lesions, possibility to obtain the mandatory biopsy (FFPE and frozen) of a metastatic lesion
  • Haemoglobin (HgB) ≥9.0 g/dL
  • Possibility to obtain the mandatory blood samples for the translational research studies.
  • Postmenopausal female defined as:
  • FDG-PET avid lesion with uptake above the background liver uptake as described below: i.e. with a marked accumulation of FDG, at least 1.5-fold greater than liver SUV mean + 2 SDs (in 3cm spherical ROI in normal right lobe of liver). If liver is abnormal, target lesion should have uptake \> 2.0 x SUV mean of blood pool in 1cm diameter ROI in descending thoracic aorta) NB:
  • Adequate renal function as shown by Serum creatinine ≤1.5 x ULN
  • ANC ≥1,500/mm3 (≥1.5 x 109/L)
  • Availability of a FFPE core of primary breast tumor
  • Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrolment.
  • Size ≥1.5cm; AND
  • Fasting serum cholesterol, triglycerides and glucose
  • Eastern Co-operative Oncology Group (ECOG) performance status ≤ 2.
  • Surgical menopause with bilateral oophorectomy NOTE: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LHRH) agonist (goserelin or leuprolide) is not permitted for induction of ovarian suppression.
  • Adequate bone marrow function as shown by:
  • Fasting serum cholesterol ≤300 mg/dL or 7.75 mmol/L
  • Recurrence while on, or within 12 months of end of adjuvant treatment with anastrozole or letrozole; OR
  • Histological or cytological confirmation of estrogen-receptor positive (ER+), HER2 negative breast cancer.

Exclusion

  • Local injections (e.g. intra-articular)
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to enrolment, uncontrolled cardiac arrhythmia
  • Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
  • Radiotherapy within four weeks prior to enrolment except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture, which can then be completed within two weeks prior to enrolment. Patients must have recovered from radiotherapy toxicities prior to enrolment.
  • Symptomatic brain metastases or other central nervous system metastases which are not controlled by local treatments.
  • Symptomatic visceral disease for example liver, pulmonary metastases or lymphangitis carcinomatosis.
  • History of non-compliance to medical regimens.
  • Symptomatic deterioration of lung function
  • Currently receiving hormone replacement therapy, unless discontinued prior to enrolment.
  • Concurrent anti-cancer treatment in another investigational trial, including hormonal therapy, immunotherapy or targeted agents other than those administered in this study.
  • Acute and chronic, active infectious disorders (except for Hepatitis B and Hepatitis C positive patients).
  • Any severe uncontrolled medical conditions such as:
  • Active bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin, LMWH and acetylsalicylic acid or equivalent, as long as the INR is ≤ 2.0).
  • Uncontrolled diabetes as defined by fasting glucose ≥ 1.5 x ULN
  • Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itraconazoleonazole, Voriconazole, Ritonavir, Telithromycin) within the last 5 days prior to enrolment.
  • Patients unwilling or unable to comply with the protocol.
  • Patients with known HIV seropositivity. Screening for HIV infection at baseline is not required
  • Inhaled sprays (e.g. obstructive airways disease)
  • Patients receiving concomitant immunosuppressive agents or chronic corticosteroid use at the time of study entry except in cases outlined below:
  • Eye drops
  • Stable low dose of corticosteroids for at least two weeks before enrolment
  • Topical applications (e.g. rash)
  • Acute and chronic, active infectious disorders and non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy.
  • Patients with only non-measurable lesions by FDG-PET/CT (e.g. pleural effusion, ascites etc.).
  • HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).