Analysis of Tumor Tissue and Circulating Genetic Material in the Blood to Obtain Further Insight in the Effectiveness of Everolimus When Combined With Exemestane

NCT02109913 | Unknown DMC

• 2 other identifiers: EudraCT 2013-004120-11BOOG 2013-06
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 28

Brief Summary

The purpose of this study is to determine whether biomarkers could be found to gain more insight in tumor characteristics in order to predict which patients will have a high chance of a long progression-free survival. Postmenopausal patients with advanced metastatic breast cancer who have progressed on anastrozole or letrozole will be eligible for this study.

Conditions

Hormone Receptor Positive Malignant Neoplasm of Breast; Metastatic Breast Cancer

Keywords

Breast Cancer; metastatic; hormone receptor positive; everolimus; biomarker

Outcome Measures

Primary Outcomes (2)

• Biomarker Evaluation from Primary Tumor Tissue, New Tumor Biopsies and Blood Samples

  Biomarker evaluation to gain more insight in tumor characteristics in order to predict which patients will have a high chance of a long progression-free survival. For biomarker evaluation, primary tumor tissue, new tumor tissue Biopsies and blood samples will be analysed for activated members of the PI3K pathway by immunohistochemistry and phosphoproteomics, and for the incidence of mutations in the PI3K pathway. The findings will be compared with the outcome of treatment and with the results from other studies.

  Before start therapy until progression (expected average until progression: 11 months)

• Progression-free survival

  Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression. Progressive disease will be assessed by radiological assessment or, if clearly stated in the patient's file, by clear clinical signs.

  From start therapy until first reported progression (expected average until progression: 11 months)

Secondary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  From start therapy until 28 days after progression (expected average until progression: 11 months)

Study Arms (1)

Everolimus plus exemestane

OTHER

Biomarker study in patients receiving standard treatment

Drug: Everolimus plus Exemestane

Interventions

Everolimus plus Exemestane DRUG

Everolimus 10mg, oral, daily; exemestane 25 mg, oral, daily. Number of Cycles: until progression or unacceptable toxicity develops. From all patients, 4 additional blood samples, 6ml each, will be collected and an optional tumor biopsy will be taken, if eligible.

Also known as: Afinitor, RAD001, CAS number 159351-69-6, EV Substance Code SUB02065MIG

Everolimus plus 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 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. Postmenopausal status is defined either by:
• Age ≥ 55 years and one year or more of amenorrhea
• Age \< 55 years and one year or more of amenorrhea, with an estradiol assay \< 40 pg/ml
• Surgical menopause with bilateral oophorectomy
• Disease refractory to NSAI, defined as:
• a. Recurrence while on or within 12 months of end of adjuvant treatment with letrozole or anastrozole, or b. Progression while on or within one month of end of letrozole or anastrozole treatment for advanced breast cancer (locally advanced or metastatic )
• Note: Letrozole or anastrozole do not have to be the last treatment prior to enrollment. Other prior anticancer therapy, e.g. tamoxifen, fulvestrant are allowed. Patients must have recovered to grade 1 or better from any adverse events (except alopecia) related to previous therapy prior to enrollment.
• Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrollment.
• Note: There are no restrictions as to the last systemic therapy prior to enrollment.
• Adequate bone marrow and coagulation function as shown by:
• Absolute neutrophil count (ANC) ≥ 1.5 ×109/L
• Platelets ≥ 100 ×109/L
• Hemoglobin (Hgb) ≥ 5.6 mmol/L

You may not qualify if:

• HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
• Previous treatment with mTOR (mammalian target of rapamycin) inhibitors.
• Radiotherapy within four weeks prior to enrollment 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 enrollment. Patients must have recovered from radiotherapy toxicities prior to enrollment.
• Currently receiving hormone replacement therapy, unless discontinued prior to enrollment.
• Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below:
• Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed.
• Patients on stable low dose of corticosteroids for at least two weeks before enrollment are allowed in case of treatment of brain metastases.
• Bilateral diffuse lymphangitic carcinomatosis or metastasis of the lung as the only manifestation of disease (\>50% of lung involvement), evidence of metastases estimated as more than a third of the liver as defined by sonogram and/or CT scan.
• Patients with a known history of HIV seropositivity.
• Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid or equivalent, as long as the INR is ≤ 2.0)
• Any severe and / or uncontrolled medical conditions such as:
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to enrollment, serious uncontrolled cardiac arrhythmia
• Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 × ULN
• Acute and chronic, active infectious disorders (except for hepatitis B and C positive patients) and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy
• 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)

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Borstkanker Onderzoek Groep: collaborator
• Novartis: collaborator

Study Sites (28)

VU University Medical Center

Amsterdam, North Holland, 1007 MB, Netherlands

Location

Flevoziekenhuis

Almere Stad, Netherlands

Location

BovenIJ Ziekenhuis

Amsterdam, Netherlands

Location

The Netherlands Cancer Institute

Amsterdam, Netherlands

Location

Gelre

Apeldoorn, Netherlands

Location

Rijnstate Ziekenhuis

Arnhem, Netherlands

Location

Amphia Ziekenhuis

Breda, Netherlands

Location

Reinier de Graaf Groep

Delft, Netherlands

Location

Gemini

Den Helder, Netherlands

Location

Deventer Ziekenhuis

Deventer, Netherlands

Location

Maxima Medisch Centrum

Eindhoven, Netherlands

Location

Groene Hart Ziekenhuis

Gouda, Netherlands

Location

Tergooi ziekenhuizen

Hilversum, Netherlands

Location

Spaarne Ziekenuis

Hoofddorp, Netherlands

Location

MC Leeuwarden

Leeuwarden, Netherlands

Location

LUMC

Leiden, Netherlands

Location

Canisius Ziekenhuis

Nijmegen, Netherlands

Location

Bravis

Roosendaal and Bergen Op Zoom, Netherlands

Location

Erasmus University Medical Center

Rotterdam, Netherlands

Location

Ikazia

Rotterdam, Netherlands

Location

Vlietland

Schiedam, Netherlands

Location

Orbis MC

Sittard, Netherlands

Location

Haga

The Hague, Netherlands

Location

MC Haaglanden

The Hague, Netherlands

Location

Elisabeth - Tweesteden

Tilburg, Netherlands

Location

UMC Utrecht

Utrecht, Netherlands

Location

VieCuri

Venray, Netherlands

Location

Isala

Zwolle, Netherlands

Location

Related Publications (3)

• Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. doi: 10.1056/NEJMoa1109653. Epub 2011 Dec 7.

  PMID: 22149876 BACKGROUND

• Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. doi: 10.1007/s12325-013-0060-1. Epub 2013 Oct 25.

  PMID: 24158787 BACKGROUND

• Lauring J, Park BH, Wolff AC. The phosphoinositide-3-kinase-Akt-mTOR pathway as a therapeutic target in breast cancer. J Natl Compr Canc Netw. 2013 Jun 1;11(6):670-8. doi: 10.6004/jnccn.2013.0086.

  PMID: 23744866 BACKGROUND

Related Links

• EU Clinical Trials Register
• Dutch Breast Cancer Research Group (Borstkanker Onderzoek Groep; BOOG)
• VU University Medical Center

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Everolimus; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Epie Boven, Prof.dr. MD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof dr Verheul, MD

Study Record Dates

• First Submitted: April 2, 2014
• First Posted: April 10, 2014
• Study Start: March 1, 2014
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: October 14, 2019

Record last verified: 2019-10

Locations

NL (28)