Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab (IMPROVE)

November 8, 2017 updated by: iOMEDICO AG

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
85

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Baden-Wuerttemberg
      • Freiburg, Baden-Wuerttemberg, Germany, 79108
        • iOMEDICO AG

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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)
Drug: Bevacizumab
administered as combined therapy with Capecitabine
Other Names:
  • Avastin®
Drug: Capecitabine
administered as combined therapy with Bevacizumab
Drug: Everolimus
administered as combined therapy with Exemestane
Other Names:
  • Afinitor®
Drug: Exemestane
administered as combined therapy with Everolimus
Other: Patient questionaires
Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference
Other Names:
  • Papient reported outcome
  • Patients' preference
Experimental: 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)
Drug: Bevacizumab
administered as combined therapy with Capecitabine
Other Names:
  • Avastin®
Drug: Capecitabine
administered as combined therapy with Bevacizumab
Drug: Everolimus
administered as combined therapy with Exemestane
Other Names:
  • Afinitor®
Drug: Exemestane
administered as combined therapy with Everolimus
Other: Patient questionaires
Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference
Other Names:
  • Papient reported outcome
  • Patients' preference

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Patients' preference
Time Frame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Reasons for patients' preference
Time Frame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation
To evaluate reasons for preference as assessed by the patient preference questionnaire
After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation
Patient reported treatment satisfaction
Time Frame: After 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase
To compare patient reported treatment satisfaction as assessed by the treatment satisfaction questionnaire in first- and second treatment phase
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
Time Frame: 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
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
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
Time Frame: After 12 weeks of first and second treatment phase
To assess progression free survival rates after 12 weeks of therapy in first- (PFS rate 1) and second treatment phase (PFS rate 2)
After 12 weeks of first and second treatment phase
Objective response rates and disease control rates based on tumor assessment (RECIST 1.1)
Time Frame: 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)
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
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)
Safety and tolerability as measured by number of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities
Time Frame: From date of informed consent to +30 days from last application of study medication
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)
From date of informed consent to +30 days from last application of study medication
Physicians' treatment preference
Time Frame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation
To determine physicians' treatment preference as assessed by the physician preference questionnaire
After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation
Progression free survival for first and second treatment phase
Time Frame: Participants will be followed until progressive disease in boths treatment phases (expected 21 months in total)
To explore progression free survival separately for each treatment phase
Participants will be followed until progressive disease in boths treatment phases (expected 21 months in total)
Overall survival
Time Frame: Participants will be followed until death (expected median of 24 months)
To explore overall survival for each treatment arm beginning from start of respective treatment phase until end of follow-up phase
Participants will be followed until death (expected median of 24 months)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Relationship Quality of life scores / patient preference
Time Frame: 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
To explore relationship between QoL scores and patient preference (Exploratory objective)
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
iOMEDICO AG

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novartis Pharmaceuticals
Arbeitsgemeinschaft fur Internistische Onkologie

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Thomas Decker, MD, practice based oncology office Ravensburg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 31, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 28, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 22, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 13, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 8, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • iOM-12293

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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