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

NCT01626222 | Completed Phase 3

• 1 other identifier: CRAD001JDE49
• Study Type: interventional
• Target: 301
• Locations: 1 country
• Sites: 84

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.

Conditions

Metastatic Breast Cancer

Keywords

Postmenopausal; Estrogen Receptor Positive; HER2 negative; Locally Advanced; Metastatic Breast Cancer; Everolimus (RAD001); Exemestane

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) after 24 weeks of treatment

  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.

  24 weeks

Secondary Outcomes (6)

• Progression free survival (PFS) after 48 weeks of treatment

  48 weeks

• Overall Response Rate (ORR) after 48 weeks of treatment

  48 weeks

• Overall survival (OS) after 48 weeks of treatment

  48 weeks

• Safety within 48 weeks of treatment

  48 weeks

• Resource utilization

  48 weeks

Study Arms (1)

Everolimus & Exemestane

EXPERIMENTAL

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.

Drug: Exemestane; Drug: Everolimus (RAD001)

Interventions

Exemestane DRUG

Exemestane is supplied by Novartis until Everolimus is commercially available for the study setting. Afterwards the investigator will prescribe Exemestane according to the individual label. Commercially available Exemestane will be supplied as tablets of 25 mg strength for oral administration. Complete guidelines for management and administration of Exemestane can be found in the package insert. Exemestane will be dosed starting on treatment Day 1. Patients will be instructed to take 1 tablet of 25 mg Exemestane orally. Package insert instructions should be followed. On the first day of each cycle, patients will receive an adequate drug supply (before commercial availability) or a prescription (after commercial availability) for self-administration at home. The investigator must emphasize compliance and will instruct the patient to take Exemestane exactly as prescribed.

Everolimus & Exemestane

Everolimus (RAD001) DRUG

Everolimus (RAD001) is supplied by Novartis until Everolimus is commercially available for the study setting. Afterwards the investigator will prescribe Everolimus according to the individual label. Everolimus is formulated as tablets of 10 and 5 mg strength for oral administration. All study medication will be packaged into blister packs. The blisters should be opened only at the time of administration, as the drugs are both hygroscopic and light sensitive. Everolimus will be dosed starting on treatment Day 1. Patients will be instructed to take 1 tablet × 10 mg Everolimus orally with a large glass of water once daily at the same time each day with or without food. On the first day of each cycle, patients will receive an adequate drug supply (before commercial availability) or a prescription (after commercial availability) for self-administration at home. The investigator must emphasize compliance and will instruct the patient to take Everolimus exactly as prescribed.

Everolimus & Exemestane

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

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 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (84)

Novartis Investigative Site

Berlin, Germany, 12203, Germany

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Novartis Investigative Site

Mainz, Germany, 55131, Germany

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Novartis Investigative Site

Aachen, 52074, Germany

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Novartis Investigative Site

Amberg, 92224, Germany

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Novartis Investigative Site

Augsburg, 86150, Germany

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Novartis Investigative Site

Augsburg, 86156, Germany

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Novartis Investigative Site

Bergisch Gladbach, 51465, Germany

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Novartis Investigative Site

Berlin, 10367, Germany

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Novartis Investigative Site

Berlin, 10707, Germany

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Novartis Investigative Site

Berlin, 12552, Germany

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Novartis Investigative Site

Berlin, 12683, Germany

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Novartis Investigative Site

Berlin, 14169, Germany

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Novartis Investigative Site

Berlin, 14195, Germany

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Novartis Investigative Site

Bochum, 44787, Germany

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Novartis Investigative Site

Bonn, 53105, Germany

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Novartis Investigative Site

Bonn, 53111, Germany

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Novartis Investigative Site

Bottrop, 46236, Germany

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Novartis Investigative Site

Böblingen, 71032, Germany

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Novartis Investigative Site

Braunschweig, 38100, Germany

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Novartis Investigative Site

Bremen, 28209, Germany

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Novartis Investigative Site

Chemnitz, 09113, Germany

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Novartis Investigative Site

Cologne, 50935, Germany

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Novartis Investigative Site

Cologne, 50937, Germany

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Novartis Investigative Site

Donauwörth, 86609, Germany

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Novartis Investigative Site

Dresden, 01127, Germany

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Novartis Investigative Site

Düsseldorf, 40225, Germany

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Novartis Investigative Site

Erlangen, 91054, Germany

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Novartis Investigative Site

Essen, 45136, Germany

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Novartis Investigative Site

Essen, 45147, Germany

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Novartis Investigative Site

Esslingen am Neckar, 73730, Germany

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Novartis Investigative Site

Eutin, 23701, Germany

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Novartis Investigative Site

Frankfurt, 60389, Germany

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Novartis Investigative Site

Frankfurt, 60590, Germany

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Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

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Novartis Investigative Site

Fulda, 36043, Germany

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Novartis Investigative Site

Fürstenwalde, 15517, Germany

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Novartis Investigative Site

Fürth, 90766, Germany

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Novartis Investigative Site

Gera, 07548, Germany

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Novartis Investigative Site

Gerlingen, 70839, Germany

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Novartis Investigative Site

Goslar, 38642, Germany

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Novartis Investigative Site

Gütersloh, 33332, Germany

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Novartis Investigative Site

Halle, 06110, Germany

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Novartis Investigative Site

Halle, 06120, Germany

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Novartis Investigative Site

Hamburg, 20249, Germany

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Novartis Investigative Site

Hanover, 30177, Germany

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Novartis Investigative Site

Heidelberg, 69120, Germany

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Novartis Investigative Site

Jena, 07740, Germany

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Novartis Investigative Site

Kassel, 34125, Germany

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Novartis Investigative Site

Kiel, 24103, Germany

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Novartis Investigative Site

Kiel, 24105, Germany

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Novartis Investigative Site

Langen, 63225, Germany

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Novartis Investigative Site

Lemgo, 32657, Germany

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Novartis Investigative Site

Lüneburg, 21339, Germany

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Novartis Investigative Site

Magdeburg, 39120, Germany

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Novartis Investigative Site

Mannheim, 68165, Germany

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Novartis Investigative Site

Marburg, 35039, Germany

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Novartis Investigative Site

Memmingen, 87700, Germany

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Novartis Investigative Site

Mönchengladbach, 41061, Germany

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Novartis Investigative Site

Mühlhausen, 99974, Germany

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Novartis Investigative Site

Mülheim, 45468, Germany

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Novartis Investigative Site

München, 80637, Germany

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Novartis Investigative Site

München, 80638, Germany

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Novartis Investigative Site

München, 81241, Germany

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Novartis Investigative Site

München, 81377, Germany

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Novartis Investigative Site

Münster, 48149, Germany

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Novartis Investigative Site

Nuremberg, 90403, Germany

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Novartis Investigative Site

Oldenburg, 26121, Germany

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Novartis Investigative Site

Plauen-Kauschwitz, 08525, Germany

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Novartis Investigative Site

Ravensburg, 88214, Germany

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Novartis Investigative Site

Recklinghausen, 45657, Germany

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Novartis Investigative Site

Rosenheim, 83022, Germany

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Novartis Investigative Site

Rostock, 18057, Germany

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Novartis Investigative Site

Singen, 78224, Germany

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Novartis Investigative Site

Soest, 59494, Germany

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Novartis Investigative Site

Speyer, 67346, Germany

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Novartis Investigative Site

Stralsund, 18435, Germany

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Novartis Investigative Site

Stuttgart, 70178, Germany

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Novartis Investigative Site

Trier, 54290, Germany

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Novartis Investigative Site

Troisdorf, 53840, Germany

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Novartis Investigative Site

Tübingen, 72076, Germany

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Novartis Investigative Site

Velbert, 42551, Germany

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Novartis Investigative Site

Villingen-Schwenningen, 78052, Germany

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Novartis Investigative Site

Weißenfels, 06667, Germany

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Novartis Investigative Site

Wuppertal, 42105, Germany

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Related Publications (2)

• Hadji P, Stoetzer O, Decker T, Kurbacher CM, Marme F, Schneeweiss A, Mundhenke C, Distelrath A, Fasching PA, Lux MP, Luftner D, Janni W, Muth M, Kreuzeder J, Quiering C, Grischke EM, Tesch H. The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial. J Bone Oncol. 2018 Oct 2;14:010-10. doi: 10.1016/j.jbo.2018.09.010. eCollection 2019 Feb.

  PMID: 30515367 DERIVED

• Tesch H, Stoetzer O, Decker T, Kurbacher CM, Marme F, Schneeweiss A, Mundhenke C, Distelrath A, Fasching PA, Lux MP, Luftner D, Hadji P, Janni W, Muth M, Kreuzeder J, Quiering C, Taran FA. Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: Results of the single-arm, phase IIIB 4EVER trial. Int J Cancer. 2019 Feb 15;144(4):877-885. doi: 10.1002/ijc.31738. Epub 2018 Oct 30.

  PMID: 29992557 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

exemestane; Everolimus

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

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2012
• First Posted: June 22, 2012
• Study Start: June 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: February 23, 2017

Record last verified: 2017-02

Locations

DE (84)