DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



4EVER - Efficacy, Safety, Health Economics, Translational Research of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer

Information source: Novartis
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Metastatic Breast Cancer

Intervention: Exemestane (Drug); Everolimus (RAD001) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Novartis Pharmaceuticals

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

Summary

The present multi-center, open-label, single-arm study aims to evaluate the efficacy and safety, quality of life and health resources utilization in postmenopausal women with hormone receptor positive breast cancer progressing following prior therapy with non-steroidal aromatase inhibitors (NSAI) treated with the combination of Everolimus and Exemestane.

Clinical Details

Official title: A Phase IIIB, Multi-Center, Open Label Study For Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Treated With Everolimus (RAD001) in Combination With Exemestane: 4EVER - Efficacy, Safety, Health Economics, Translational Research

Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Overall Response Rate (ORR) after 24 weeks of treatment

Secondary outcome:

Progression free survival (PFS) after 48 weeks of treatment

Overall Response Rate (ORR) after 48 weeks of treatment

Overall survival (OS) after 48 weeks of treatment

Safety within 48 weeks of treatment

Resource utilization

Health-related quality of life

Detailed description: In light of the need for new treatment options for postmenopausal, hormone receptor positive, HER2 negative women after failure of prior non-steroidal aromatase inhibitor (NSAI) therapy, the BOLERO-2 trial was performed and demonstrated significant efficacy of the combinatorial treatment of Everolimus and Exemestane compared to an Exemestane monotherapy in this setting. In this randomized, double blind, placebo-controlled trial a statistically significant improvement in progression-free survival (PFS) by adding Everolimus to exemestane versus Exemestane alone was reported. Adding Everolimus determined a 2. 4-fold prolongation in PFS from 3. 2 up to 7. 4 months and so lowered the risk of cancer progression by 56% for these women. These findings were confirmed by an independent assessment (4. 1 vs. 11. 0 months, risk reduction: 64%). The quality of life data shows positive trend in the Everolimus plus Exemestane treatment arm. (Baselga 2011, Hortobagyi 2011). Thus, the benefit of the combinatorial treatment versus Exemestane monotherapy was shown in a defined patient population under controlled conditions. The primary objective of this trial to assess the Overall Response Rate (ORR) in postmenopausal women with hormone receptor positive breast cancer progressing following prior therapy with NSAIs treated with the combination of Everolimus and Exemestane. The secondary objectives include, Progression free survival (PFS), Overall survival (OS), Safety, Change in Quality of life scores over time, Health resource utilization. The exploratory objectives reflect scientific interest within the treatment of metastatic breast cancer and are to be modified, if applicable, according to the current scientific state of the art at the time of actual analysis. These include: the influence of age, performance status, cancer activity and inflammation on anxiety and depression; changes in serum bone-turnover biomarkers; Pharmacogenetics of Everolimus in patients with advanced breast cancer; presence and molecular characteristics of Circulating Tumor Cells; correlation of response to Exemestane/Everolimus with Proteomic analysis. The present national, multi-center, open-label, single-arm study aims to evaluate the efficacy and safety, quality of life and health resources utilization of the combination of Everolimus and Exemestane in a broader patient population compared to BOLERO-2, i. e. without limitations as to the number of previous chemotherapy lines, the time point of progression after NSAI therapy, and the previous endocrine therapy as patients under Exemestane monotherapy may be enrolled. Since the combination was shown to significantly improve PFS in the previous BOLERO-2 trial, for ethical reasons no endocrine comparator drugs will be investigated in the present study, due to the low efficacy of Exemestane monotherapy (PFS 3. 2 months).

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Main Inclusion criteria: Metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy or any other non-systemic treatment. Histological or cytological confirmation of estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer Postmenopausal women. Disease progression following prior therapy with non steroidal aromatase inhibitors (NSAI), defined as: Recurrence while on, or following completion of an adjuvant treatment with Letrozole or Anastrozole, or Progression while on or following completion of Letrozole or Anastrozole treatment for ABC/MBC. Radiological evidence of recurrence or progression on last systemic therapy prior to enrollment. Patients must have at least one lesion that can be accurately measured or bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease. Written informed consent obtained before any screening procedure and according to local guidelines. Other protocol defined inclusion criteria apply. Main Exclusion criteria: HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive). Patients with only non-measurable lesions other than bone metastasis (e. g. pleural effusion, ascites etc.). Previous treatment with mTOR inhibitors or known hypersensitivity to mTOR inhibitors. Symptomatic brain or other CNS metastases. Previously treated brain metastases are allowed provided the patient is free of symptoms, prior radiotherapy for brain metastasis was more than four weeks before enrollment and the dose of corticosteroids is low (i. e. ≤ 10 mg/d Prednisolone equivalent) and stable for at least two weeks prior to enrollment. Patients with Hepatitis B or C or with a history of Hepatitis B or C. Patients unwilling to or unable to comply with the protocol. Other protocol defined exclusion criteria apply.

Locations and Contacts

Novartis Investigative Site, Aachen 52074, Germany

Novartis Investigative Site, Amberg 92224, Germany

Novartis Investigative Site, Augsburg 86150, Germany

Novartis Investigative Site, Augsburg 86156, Germany

Novartis Investigative Site, Bergisch Gladbach 51465, Germany

Novartis Investigative Site, Berlin 10707, Germany

Novartis Investigative Site, Berlin 14169, Germany

Novartis Investigative Site, Berlin 12203, Germany

Novartis Investigative Site, Berlin 12552, Germany

Novartis Investigative Site, Berlin 12683, Germany

Novartis Investigative Site, Berlin 14195, Germany

Novartis Investigative Site, Berlin 10367, Germany

Novartis Investigative Site, Bochum 44787, Germany

Novartis Investigative Site, Bonn 53105, Germany

Novartis Investigative Site, Bonn 53111, Germany

Novartis Investigative Site, Bottrop 46236, Germany

Novartis Investigative Site, Braunschweig 38100, Germany

Novartis Investigative Site, Bremen 28209, Germany

Novartis Investigative Site, Böblingen 71032, Germany

Novartis Investigative Site, Chemnitz 09113, Germany

Novartis Investigative Site, Donauwoerth 86609, Germany

Novartis Investigative Site, Dresden 01127, Germany

Novartis Investigative Site, Duesseldorf 40225, Germany

Novartis Investigative Site, Erlangen 91054, Germany

Novartis Investigative Site, Essen 45136, Germany

Novartis Investigative Site, Essen 45147, Germany

Novartis Investigative Site, Esslingen 73730, Germany

Novartis Investigative Site, Eutin 23701, Germany

Novartis Investigative Site, Frankfurt 60389, Germany

Novartis Investigative Site, Frankfurt 60590, Germany

Novartis Investigative Site, Freiburg 79106, Germany

Novartis Investigative Site, Fuerstenwalde 15517, Germany

Novartis Investigative Site, Fuerth 90766, Germany

Novartis Investigative Site, Fulda 36043, Germany

Novartis Investigative Site, Gera 07548, Germany

Novartis Investigative Site, Gerlingen 70839, Germany

Novartis Investigative Site, Goslar 38642, Germany

Novartis Investigative Site, Gütersloh 33332, Germany

Novartis Investigative Site, Halle/'Saale 06120, Germany

Novartis Investigative Site, Halle 06110, Germany

Novartis Investigative Site, Hamburg 20249, Germany

Novartis Investigative Site, Hannover 30177, Germany

Novartis Investigative Site, Heidelberg 69120, Germany

Novartis Investigative Site, Jena 07740, Germany

Novartis Investigative Site, Kassel 34125, Germany

Novartis Investigative Site, Kiel 24103, Germany

Novartis Investigative Site, Kiel 24105, Germany

Novartis Investigative Site, Koeln 50935, Germany

Novartis Investigative Site, Köln 50937, Germany

Novartis Investigative Site, Langen 63225, Germany

Novartis Investigative Site, Lemgo 32657, Germany

Novartis Investigative Site, Lüneburg 21339, Germany

Novartis Investigative Site, Magdeburg 39120, Germany

Novartis Investigative Site, Mainz 55131, Germany

Novartis Investigative Site, Mannheim 68165, Germany

Novartis Investigative Site, Marburg 35039, Germany

Novartis Investigative Site, Memmingen 87700, Germany

Novartis Investigative Site, Muelheim 45468, Germany

Novartis Investigative Site, Muenchen 81377, Germany

Novartis Investigative Site, Muenchen 81241, Germany

Novartis Investigative Site, Muenchen 80637, Germany

Novartis Investigative Site, Muenster 48149, Germany

Novartis Investigative Site, Mönchengladbach 41061, Germany

Novartis Investigative Site, Mühlhausen 99974, Germany

Novartis Investigative Site, München 80638, Germany

Novartis Investigative Site, Nuernberg 90403, Germany

Novartis Investigative Site, Oldenburg 26121, Germany

Novartis Investigative Site, Plauen-Kauschwitz 08525, Germany

Novartis Investigative Site, Ravensburg 88214, Germany

Novartis Investigative Site, Recklinghausen 45657, Germany

Novartis Investigative Site, Rosenheim 83022, Germany

Novartis Investigative Site, Rostock 18057, Germany

Novartis Investigative Site, Singen 78224, Germany

Novartis Investigative Site, Soest 59494, Germany

Novartis Investigative Site, Speyer 67346, Germany

Novartis Investigative Site, Stralsund 18435, Germany

Novartis Investigative Site, Stuttgart 70178, Germany

Novartis Investigative Site, Trier 54290, Germany

Novartis Investigative Site, Troisdorf 53840, Germany

Novartis Investigative Site, Tuebingen 72076, Germany

Novartis Investigative Site, Velbert 42551, Germany

Novartis Investigative Site, Villingen-Schwenningen 78052, Germany

Novartis Investigative Site, Weißenfels 06667, Germany

Novartis Investigative Site, Wuppertal 42105, Germany

Additional Information

Starting date: June 2012
Last updated: April 26, 2015

Page last updated: August 20, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017