Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab

NCT ID: NCT02248571

Last Updated: 2017-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

85 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-08-31

Study Completion Date

2017-09-30

Brief Summary

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This is a clinical trial with a crossover design to determine patients' preference for capecitabine in combination with bevacizumab or everolimus in combination with exemestane for advanced breast cancer patients and to evaluate, if any combination is associated with a better quality of life.

To identify patients' preference for either therapy in this trial, patients without disease progression or other reasons for early discontinuation will be asked for their treatment preference and their treatment satisfaction. To correlate patients' preference with other patient reported outcomes (PROs), quality of life (QoL) will be assessed at baseline and throughout the study, using dedicated questionnaires.

With similarly active treatment options, it is of utmost importance to identify the treatment that has the least negative impact on the patients' quality of life.

Detailed Description

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Conditions

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Breast Cancer Recurrent HER2/Neu-negative Carcinoma of Breast Hormone Receptor Positive Malignant Neoplasm of Breast

Keywords

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breast cancer advanced inoperable metastatic HER2/neu-negative hormone receptor positive HR+ female postmenopausal

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Arm A

Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase)

Dosing (treatment cycle: 21days):

1. Capecitabine: 1000 mg/m2 orally applied twice daily as combined 150 mg and 500 mg tablets on days 1 to 14 of each 21-day cycle, followed by a seven day rest period (i.e. off-treatment) --- Bevacizumab: 15 mg/kg intravenously applied once every three weeks (i.e. 5 mg/kg/wk dose equivalent)
2. Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet

Patient questionaires to assess patient reported outcome and patients' preference will be completed at four specific time points during study treatment (two timepoints in each treatment phase)

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

administered as combined therapy with Capecitabine

Capecitabine

Intervention Type DRUG

administered as combined therapy with Bevacizumab

Everolimus

Intervention Type DRUG

administered as combined therapy with Exemestane

Exemestane

Intervention Type DRUG

administered as combined therapy with Everolimus

Patient questionaires

Intervention Type OTHER

Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference

Arm B

Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase)

Dosing (treatment cycle: 21days):

1. Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet
2. Capecitabine: 1000 mg/m2 orally applied twice daily as combined 150 mg and 500 mg tablets on days 1 to 14 of each 21-day cycle, followed by a seven day rest period (i.e. off-treatment) --- Bevacizumab: 15 mg/kg intravenously applied once every three weeks (i.e. 5 mg/kg/wk dose equivalent)

Patient questionaires to assess patient reported outcome and patients' preference will be completed at four specific time points during study treatment (two timepoints in each treatment phase)

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

administered as combined therapy with Capecitabine

Capecitabine

Intervention Type DRUG

administered as combined therapy with Bevacizumab

Everolimus

Intervention Type DRUG

administered as combined therapy with Exemestane

Exemestane

Intervention Type DRUG

administered as combined therapy with Everolimus

Patient questionaires

Intervention Type OTHER

Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference

Interventions

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Bevacizumab

administered as combined therapy with Capecitabine

Intervention Type DRUG

Capecitabine

administered as combined therapy with Bevacizumab

Intervention Type DRUG

Everolimus

administered as combined therapy with Exemestane

Intervention Type DRUG

Exemestane

administered as combined therapy with Everolimus

Intervention Type DRUG

Patient questionaires

Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference

Intervention Type OTHER

Other Intervention Names

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Avastin® Afinitor® Papient reported outcome Patients' preference

Eligibility Criteria

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Inclusion Criteria

Written informed consent must be obtained prior to any study specific procedure.

1. Adult women (≥ 18 years of age)
2. . Postmenopausal status

The investigator must confirm postmenopausal status. 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 and postmenopausal levels of follicle stimulating hormone (FSH) and Luteinizing hormone (LH) per local institutional standards
* Prior hysterectomy and has postmenopausal levels of FSH and LH per local institutional standards
* Surgical menopause with bilateral oophorectomy
* For women with therapy-induced amenorrhea, oophorectomy or serial measurements of FSH and / or estradiol are needed to ensure postmenopausal status.

Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression.
3. Pathologically confirmed HER2/neu-negative, ER/PR positive inoperable or metastatic adenocarcinoma of the breast
4. Indication for systemic palliative targeted therapy / first line chemotherapy after failure of at least one non-steroidal aromatase inhibitor therapy at any time during the disease course (no restriction regarding the number of previous endocrine lines)
5. No indication for other chemotherapeutic treatment including Taxanes or Anthracyclines
6. Measurable or non-measurable disease as per RECIST 1.1
7. Adequate bone marrow, liver and renal function (according to current SmPCs of both treatment regimens)
8. ECOG performance status 0-2
9. Fluent German (spoken and written) language

Exclusion Criteria

1. Prior palliative cytotoxic chemotherapies
2. Prior exposure to mTOR-Inhibitors (prior treatment with exemestane is allowed)
3. Concomitant antihormonal therapies, other than study medication
4. Symptomatic visceral metastases (as deemed by the investigator)
5. Uncontrolled CNS metastases
6. Unstable skeletal metastases
7. Medically uncontrolled cardiovascular diseases (e.g. uncontrolled hypertension)
8. Medically uncontrolled diabetes mellitus
9. Severe hepatic impairment (Child-Pugh C)
10. Inadequate organ function as specified below:

* Hemoglobin \< 9.0 g/dl
* Absolute neutrophil count (ANC) \<1,5 x109/L
* Platelets \<100 x109/L
* Creatinine clearance \< 30ml/min \[Cockcroft and Gault\]
11. Known HIV infection or chronic hepatitis B or C or history of hepatitis B or C
12. Known dihydropyrimidine dehydrogenase (DPD) deficiency
13. Any other contraindications to the study drugs used or their excipients according to current SmPCs
14. Concomitant use of immunosuppressive agents or chronic use of systemic corticosteroids
15. Use of any other concomitant medication known to interfere with the study drugs
16. Use of concomitant medication known to interfere with the study results (e.g. hormonal therapy) during the whole study duration
17. Premenopausal patients
18. Pregnant or breast feeding patients
19. Participation in additional parallel interventional drug or device studies within four weeks before start of study.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Arbeitsgemeinschaft fur Internistische Onkologie

OTHER

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

iOMEDICO AG

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas Decker, MD

Role: PRINCIPAL_INVESTIGATOR

practice based oncology office Ravensburg

Locations

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iOMEDICO AG

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 22149876 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24158787 (View on PubMed)

Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005 Feb 1;23(4):792-9. doi: 10.1200/JCO.2005.05.098.

Reference Type BACKGROUND
PMID: 15681523 (View on PubMed)

Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. doi: 10.1200/JCO.2010.28.0982. Epub 2011 Mar 7.

Reference Type BACKGROUND
PMID: 21383283 (View on PubMed)

Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, Gschwend JE, De Giorgi U, Parikh O, Hawkins R, Sevin E, Negrier S, Khan S, Diaz J, Redhu S, Mehmud F, Cella D. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014 May 10;32(14):1412-8. doi: 10.1200/JCO.2013.50.8267. Epub 2014 Mar 31.

Reference Type BACKGROUND
PMID: 24687826 (View on PubMed)

Other Identifiers

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iOM-12293

Identifier Type: -

Identifier Source: org_study_id