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Breast Cancer RecurrentPhase 4IMPROVENCT02248571

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

A Phase 4 study testing Bevacizumab, Capecitabine and Everolimus in people with Breast Cancer Recurrent and HER2/Neu-negative Carcinoma of Breast, run by iOMEDICO AG at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Bevacizumab, Capecitabine and Everolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
85 participants
Where
1 siteGermany
Study dates
Aug 2014to 30 Sep 2017
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 17Show fewer
  • 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)
  • ECOG performance status 0-2
  • Fluent German (spoken and written) language

Who cannot join

  • 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
Show all 23Show fewer
  • 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
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Any other contraindications to the study drugs used or their excipients according to current SmPCs
  • Concomitant use of immunosuppressive agents or chronic use of systemic corticosteroids
  • Use of any other concomitant medication known to interfere with the study drugs
  • Use of concomitant medication known to interfere with the study results (e.g. hormonal therapy) during the whole study duration
  • Premenopausal patients
  • Pregnant or breast feeding patients
  • Participation in additional parallel interventional drug or device studies within four weeks before start of study.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • iOMEDICO AG

    Freiburg im Breisgau, Baden-Wurttemberg, 79108

Other trials in Germany

About this study

Official title: An Open Label, randomIzed Controlled Prospective Multicenter Two Arm Phase IV Trial to Determine Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab for Advanced (Inoperable or Metastatic) HER2-negative Hormone Receptor Positive Breast Cancer

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.

Being tested
Bevacizumab, Capecitabine, Everolimus, Exemestane, Patient questionaires
Keywords
breast cancer, advanced, inoperable, metastatic, HER2/neu-negative, hormone receptor positive, HR+, female, postmenopausal
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabDrug

    Also called Avastin®

    administered as combined therapy with Capecitabine

  • CapecitabineDrug

    administered as combined therapy with Bevacizumab

  • EverolimusDrug

    Also called Afinitor®

    administered as combined therapy with Exemestane

  • ExemestaneDrug

    administered as combined therapy with Everolimus

  • Patient questionairesOther

    Also called Papient reported outcome, Patients' preference

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

Study groups in NCT02248571
Study groupRoleWhat they receive
Arm AExperimentalBevacizumab 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)
Receives: Drug: Bevacizumab; Drug: Capecitabine; Drug: Everolimus; Drug: Exemestane; Other: Patient questionaires
Arm BExperimentalEverolimus 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)
Receives: Drug: Bevacizumab; Drug: Capecitabine; Drug: Everolimus; Drug: Exemestane; Other: Patient questionaires

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (9)

  1. Reasons for patients' preference

    To evaluate reasons for preference as assessed by the patient preference questionnaire

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

  2. Patient reported treatment satisfaction

    To compare patient reported treatment satisfaction as assessed by the treatment satisfaction questionnaire in first- and second treatment phase

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

  3. Quality of life

    To investigate differences in quality of life by the European Organization for Research and Treatment of Cancer quality of life questionnaire 30 (EORTC QLQ-C30) and EORTC QLQ-FA13 questionnaire

    Measured: 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

  4. Progression free survival rate

    To assess progression free survival rates after 12 weeks of therapy in first- (PFS rate 1) and second treatment phase (PFS rate 2)

    Measured: After 12 weeks of first and second treatment phase

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

    To assess clinical benefit by determining objective response rates and disease control rates based on tumor assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

    Measured: 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)

  6. Safety and tolerability as measured by number of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities

    To evaluate safety and tolerability throughout the study according to Common Toxicity Criteria for Adverse Effects (CTCAE) 4.03 criteria, including clinical laboratory (grades 3 or 4 - separately for hematology and biochemistry) and number of treatment-emergent AEs (safety data for pre- and post-treatment periods will be listed separately)

    Measured: From date of informed consent to +30 days from last application of study medication

  7. Physicians' treatment preference

    To determine physicians' treatment preference as assessed by the physician preference questionnaire

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

  8. Progression free survival for first and second treatment phase

    To explore progression free survival separately for each treatment phase

    Measured: Participants will be followed until progressive disease in boths treatment phases (expected 21 months in total)

  9. Overall survival

    To explore overall survival for each treatment arm beginning from start of respective treatment phase until end of follow-up phase

    Measured: Participants will be followed until death (expected median of 24 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2014 (estimated)
  2. Study startAug 2014
  3. Primary completion31 Aug 2017
  4. Study completion30 Sep 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Other
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02248571
Sponsor's protocol ID
iOM-12293
Acronym
IMPROVE
Status last verified
Nov 2017
First submitted
28 Aug 2014
Last updated
13 Nov 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 22149876

  • 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.

    PubMed 24158787

  • 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.

    PubMed 15681523

  • 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.

    PubMed 21383283

  • 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.

    PubMed 24687826

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Bevacizumab, Capecitabine and Everolimus in people with Breast Cancer Recurrent and HER2/Neu-negative Carcinoma of Breast, run by iOMEDICO AG at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patients' preference (time frame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02248571, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.

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