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

NCT02248571 | Completed Phase 4

• 1 other identifier: iOM-12293
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Patients' preference

  Patients' preference of the two treatment combinations capecitabine plus bevacizumab or everolimus in combination with exemestane after failure of standard antihormonal therapy in patients with advanced (inoperable or metastatic) HER2/neu-negative hormone receptor positive breast cancer. The preference will be ascertained using the patient preference questionnaire.

  After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation

Secondary Outcomes (9)

• Reasons for patients' preference

  After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation

• Patient reported treatment satisfaction

  After 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase

• Quality of life

  At baseline and after 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase

• Progression free survival rate

  After 12 weeks of first and second treatment phase

• Objective response rates and disease control rates based on tumor assessment (RECIST 1.1)

  Participants will be followed for the whole duration of first phase therapy, with an expected average of 12 months, plus 3 months of second phase therapy (15 months in total)

Other Outcomes (1)

• Relationship Quality of life scores / patient preference

  At baseline and after 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase

Study Arms (2)

Arm A

EXPERIMENTAL

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)

Drug: Bevacizumab; Drug: Capecitabine; Drug: Everolimus; Drug: Exemestane; Other: Patient questionaires

Arm B

EXPERIMENTAL

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)

Drug: Bevacizumab; Drug: Capecitabine; Drug: Everolimus; Drug: Exemestane; Other: Patient questionaires

Interventions

Bevacizumab DRUG

administered as combined therapy with Capecitabine

Also known as: Avastin®

Arm A; Arm B

Capecitabine DRUG

administered as combined therapy with Bevacizumab

Arm A; Arm B

Everolimus DRUG

administered as combined therapy with Exemestane

Also known as: Afinitor®

Arm A; Arm B

Exemestane DRUG

administered as combined therapy with Everolimus

Arm A; Arm B

Patient questionaires OTHER

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

Also known as: Papient reported outcome, Patients' preference

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• Written informed consent must be obtained prior to any study specific procedure.
• Adult women (≥ 18 years of age)
• 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.
• Pathologically confirmed HER2/neu-negative, ER/PR positive inoperable or metastatic adenocarcinoma of the breast
• 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)
• No indication for other chemotherapeutic treatment including Taxanes or Anthracyclines
• Measurable or non-measurable disease as per RECIST 1.1
• Adequate bone marrow, liver and renal function (according to current SmPCs of both treatment regimens)

You may not qualify if:

• Prior palliative cytotoxic chemotherapies
• Prior exposure to mTOR-Inhibitors (prior treatment with exemestane is allowed)
• Concomitant antihormonal therapies, other than study medication
• Symptomatic visceral metastases (as deemed by the investigator)
• Uncontrolled CNS metastases
• Unstable skeletal metastases
• Medically uncontrolled cardiovascular diseases (e.g. uncontrolled hypertension)
• Medically uncontrolled diabetes mellitus
• Severe hepatic impairment (Child-Pugh C)
• 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 \[Cockcroft and Gault\]
• Known HIV infection or chronic hepatitis B or C or history of hepatitis B or C

Sponsors & Collaborators

• iOMEDICO AG: lead
• Arbeitsgemeinschaft fur Internistische Onkologie: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

iOMEDICO AG

Freiburg im Breisgau, Baden-Wurttemberg, 79108, Germany

Location

Related Publications (5)

• 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

• 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.

  PMID: 15681523 BACKGROUND

• 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.

  PMID: 21383283 BACKGROUND

• 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.

  PMID: 24687826 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Bevacizumab; Capecitabine; 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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Thomas Decker, MD

  practice based oncology office Ravensburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2014
• First Posted: September 25, 2014
• Study Start: August 1, 2014
• Primary Completion: August 31, 2017
• Study Completion: September 30, 2017
• Last Updated: November 13, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)