Pet Imaging as a Biomarker in Hormone Refractory postmenopausaL Women

NCT02028364 | Completed Phase 2

• 2 other identifiers: IJB-BCTL:201203062012-004860-22
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Locally advanced breast cancer; HER2 negative; NSAI refractory; Metastatic breast cancer; Estrogen-receptor positive (ER+)

Outcome Measures

Primary Outcomes (1)

• PFS based on RECIST criteria 1.1.

  To evaluate if early metabolic response (MR) using FDG-PET/CT is associated with progression free survival (PFS) in ER+, HER2 negative ABC or MBC patients treated with exemestane plus everolimus.

  2.5 years from FPI

Secondary Outcomes (3)

• Overall survival (OS)

  2.5 years from first patient in

• * Proportion of FDG-PET/CT metabolic non-responders/FDG-PET/CT metabolic responders * Estimate the most suitable second FDG-PET/CT time point (2 weeks versus 4 weeks after initiation of treatment).

  Baseline, day 14, Day 28 and at progression

• Biomarker Assessment

  baseline, day 14, day 28, every 12 weeks and at progression

Study Arms (1)

Everolimus given in conjunction with exemestane

EXPERIMENTAL

Everolimus 10mg orally daily given in conjunction with exemestane 25mg orally daily until disease progression or treatment discontinuation for any other reasons.

Drug: Everolimus; Drug: Exemestane

Interventions

Everolimus DRUG

10mg orally daily

Also known as: Afinitor

Everolimus given in conjunction with exemestane

Exemestane DRUG

25mg orally daily

Also known as: Aromasin, Exemestane Teva, Exemestane Sandoz, Exemarom,Exemestane Mylan, Exemestane Accord Healthcare

Everolimus given in conjunction with exemestane

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 locally advanced or metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy.
• Histological or cytological confirmation of estrogen-receptor positive (ER+), HER2 negative breast cancer.
• Postmenopausal female defined as:
• Age ≥55 years and one year or more of amenorrhoea
• Age \<55 years and one year or more of amenorrhoea, with an estradiol assay \<20pg/ml
• 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.
• Breast cancer that is refractory to non-steroidal aromatase inhibitors (NSAI) (i.e. anastrozole or letrozole) defined as:
• Recurrence while on, or within 12 months of end of adjuvant treatment with anastrozole or letrozole; OR
• 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.
• FDG-PET measurable disease defined as: at least one target lesion fulfilling following criteria:
• Size ≥1.5cm; AND
• 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:
• The target lesion can be a bone metastasis if it fulfils the above mentioned criteria.

You may not qualify if:

• HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
• Patients with only non-measurable lesions by FDG-PET/CT (e.g. pleural effusion, ascites etc.).
• Symptomatic visceral disease for example liver, pulmonary metastases or lymphangitis carcinomatosis.
• Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
• Another malignancy within 5 years prior to enrolment, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer.
• 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.
• Currently receiving hormone replacement therapy, unless discontinued prior to enrolment.
• Symptomatic brain metastases or other central nervous system metastases which are not controlled by local treatments.
• Patients receiving concomitant immunosuppressive agents or chronic corticosteroid use at the time of study entry except in cases outlined below:
• Topical applications (e.g. rash)
• Inhaled sprays (e.g. obstructive airways disease)
• Eye drops
• Local injections (e.g. intra-articular)
• Stable low dose of corticosteroids for at least two weeks before enrolment
• Patients with known HIV seropositivity. Screening for HIV infection at baseline is not required

Sponsors & Collaborators

• Jules Bordet Institute: lead
• Novartis: collaborator

Study Sites (5)

institut Jules Bordet

Brussels, 1000, Belgium

Location

Cliniques Universtaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU Ambroise Paré

Mons, 7000, Belgium

Location

Clinique et Maternité Sainte Elisabeth

Namur, 5000, Belgium

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; exemestane

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Andrea Gombos, MD

  Insitut Jules Bordet

  PRINCIPAL INVESTIGATOR

• Patrick Flamen, MD

  Jules Bordet Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2013
• First Posted: January 7, 2014
• Study Start: January 12, 2014
• Primary Completion: July 6, 2021
• Study Completion: August 9, 2021
• Last Updated: August 24, 2023

Record last verified: 2023-08

Locations

BE (5)