4EVER - Efficacy, Safety, Health Economics, Translational Research of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer (MACS2096)
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ClinicalTrials.gov Identifier: NCT01626222 |
Recruitment Status
:
Completed
First Posted
: June 22, 2012
Last Update Posted
: February 23, 2017
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Tracking Information | ||||
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First Submitted Date ICMJE | June 20, 2012 | |||
First Posted Date ICMJE | June 22, 2012 | |||
Last Update Posted Date | February 23, 2017 | |||
Study Start Date ICMJE | June 2012 | |||
Actual Primary Completion Date | November 2013 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Overall Response Rate (ORR) after 24 weeks of treatment [ Time Frame: 24 weeks ] The Overall response rate (ORR) is the proportion of patients with a best overall response of confirmed complete (CR) or partial (PR) response by Week 24. The best overall response is determined from the sequence of investigator overall lesion responses according to RECIST 1.1. To be assigned a best overall response of CR at least two determinations of CR at least 4 weeks apart before progression are required. To be assigned a best overall response of PR at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) are required.
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Original Primary Outcome Measures ICMJE | Same as current | |||
Change History | Complete list of historical versions of study NCT01626222 on ClinicalTrials.gov Archive Site | |||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | |||
Current Other Outcome Measures ICMJE | Not Provided | |||
Original Other Outcome Measures ICMJE | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | 4EVER - Efficacy, Safety, Health Economics, Translational Research of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer | |||
Official Title ICMJE | 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 | |||
Brief 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. | |||
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). |
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Study Type ICMJE | Interventional | |||
Study Phase | Phase 3 | |||
Study Design ICMJE | Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Metastatic Breast Cancer | |||
Intervention ICMJE |
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Study Arms | Experimental: Everolimus & Exemestane
This study will be performed in 300 postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer progressing following prior therapy with non-steroidal aromatase inhibitors (NSAI) as defined by: 1. Recurrence while on or after completion of an adjuvant treatment including Letrozole or Anastrozole, or 2. Progression while on or following the completion of Letrozole or Anastrozole treatment for locally advanced or metastatic breast cancer. Except for prior use of mTOR inhibitors, there are no restrictions as to the last anticancer treatment prior to enrollment. Patients must have documented evidence of recurrence or progression on last therapy prior to enrollment. Written informed consent must be obtained prior to any screening procedures. The investigator or designee must ensure that only patients who meet all the following inclusion and none of the exclusion criteria are offered enrollment in the study.
Interventions:
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
301 | |||
Original Estimated Enrollment ICMJE |
300 | |||
Actual Study Completion Date | November 2013 | |||
Actual Primary Completion Date | November 2013 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | 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. |
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Sex/Gender |
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Ages | 18 Years and older (Adult, Senior) | |||
Accepts Healthy Volunteers | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Germany | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01626222 | |||
Other Study ID Numbers ICMJE | CRAD001JDE49 | |||
Has Data Monitoring Committee | No | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement | Not Provided | |||
Responsible Party | Novartis ( Novartis Pharmaceuticals ) | |||
Study Sponsor ICMJE | Novartis Pharmaceuticals | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | Novartis | |||
Verification Date | February 2017 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |