- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02248571
Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab (IMPROVE)
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
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Baden-Wuerttemberg
-
Freiburg, Baden-Wuerttemberg, Germany, 79108
- iOMEDICO AG
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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)
- ECOG performance status 0-2
- Fluent German (spoken and written) language
Exclusion Criteria:
- 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
- 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.
Study Plan
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 |
Intervention / Treatment |
---|---|
Experimental: Arm A
Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase) Dosing (treatment cycle: 21days):
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) |
administered as combined therapy with Capecitabine
Other Names:
administered as combined therapy with Bevacizumab
administered as combined therapy with Exemestane
Other Names:
administered as combined therapy with Everolimus
Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference
Other Names:
|
Experimental: Arm B
Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase) Dosing (treatment cycle: 21days):
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) |
administered as combined therapy with Capecitabine
Other Names:
administered as combined therapy with Bevacizumab
administered as combined therapy with Exemestane
Other Names:
administered as combined therapy with Everolimus
Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference
Other Names:
|
What is the study measuring?
Primary Outcome Measures
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
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
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
Sponsor
Investigators
- Principal Investigator: Thomas Decker, MD, practice based oncology office Ravensburg
Publications and helpful links
General 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.
- 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. Erratum In: Adv Ther. 2014 Sep;31(9):1008-9.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms by Site
- Breast Diseases
- Neoplasms
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Capecitabine
- Bevacizumab
- Everolimus
- Exemestane
Other Study ID Numbers
- iOM-12293
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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