E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2/neu-negative, ER/PR positive inoperable or metastatic adenocarcinoma of the breast |
HER2/neu-negativer, ER/PR positiver inoperabler oder metastasiertes Adenokarzinom der Brust |
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E.1.1.1 | Medical condition in easily understood language |
HER2/neu-negative, ER/PR positive inoperable or metastatic adenocarcinoma of the breast |
HER2/neu-negativer, ER/PR positiver inoperabler oder metastasiertes Adenokarzinom der Brust |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057654 |
E.1.2 | Term | Breast cancer female |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this trial is to compare patients’ preferences of the two treatment combinations everolimus plus exemestane or capecitabine in combination with bevacizumab after failure of standard antihormonal therapy in patients with advanced (inoperable or metastatic) Her2/neu-negative hormone receptor positive breast cancer |
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E.2.2 | Secondary objectives of the trial |
• to evaluate reasons for preference as assessed by the patient preference questionnaire • to compare patient reported treatment satisfaction as assessed by the treatment satisfaction questionnaire in first- and second-line treatment • to investigate differences in quality of life by the EORTC QLQ-C30 and EORTC QLQ-FA13 questionnaire • to assess progression free survival rates after 12 weeks of therapy in first- (PFS rate 1) and second-line (PFS rate 2) • to assess clinical benefit by determining objective response rates and disease control rates based on tumor assessment as per RECIST 1.1 • to evaluate safety and tolerability throughout the study, including clinical laboratory, AEs and withdrawal of treatment due to AE • to determine physicians’ treatment preference as assessed by the physician preference questionnaire • to explore progression free survival and overall survival total and per line • to explore relationship between QoL scores and patient preference |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 FSH and 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 target 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 |
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E.4 | Principal 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 [Cockroft and Gault] 11. Known HIV infection or chronic hepatitis B or C or history of hepatitis B or C 12. Known dihydropyrimidin 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare patients’ preferences of the two treatment combinations everolimus plus exemestane or capecitabine in combination with bevacizumab after failure of standard antihormonal therapy in patients with advanced (inoperable or metastatic) Her2/neu-negative hormone receptor positive breast cancer. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The initially scheduled interim analysis will be omitted. Study data will be analyzed in the final analysis as planned based on the current number of randomized patients. The final analysis will take place once all patients have terminated trial therapy. This is planned for Q3 2017.
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E.5.2 | Secondary end point(s) |
• to evaluate reasons for preference as assessed by the patient preference questionnaire • to compare patient reported treatment satisfaction as assessed by the treatment satisfaction questionnaire in first- and second-line treatment • to investigate differences in quality of life by the EORTC QLQ-C30 and EORTC QLQ-FA13 questionnaire • to assess progression free survival rates after 12 weeks of therapy in first- (PFS rate 1) and second-line (PFS rate 2) • to assess clinical benefit by determining objective response rates and disease control rates based on tumor assessment as per RECIST 1.1 • to evaluate safety and tolerability throughout the study, including clinical laboratory, AEs and withdrawal of treatment due to AE • to determine physicians’ treatment preference as assessed by the physician preference questionnaire • to explore progression free survival and overall survival total and per line Exploratory objectives are: • to explore relationship between QoL scores and patient preference |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The initially scheduled interim analysis will be omitted. Study data will be analyzed in the final analysis as planned based on the current number of randomized patients. The final analysis will take place once all patients have terminated trial therapy. This is planned for Q3 2017. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient preference The primary objective of the study is to compare patients’ preferences of the two treatment combinations everolimus plus exemestane or capecitabine in combination with bevacizumab 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, assessed after 12 weeks of second line therapy. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Sequential application of study medications |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 39 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Data collection will be stopped after the end of safety follow-up (LPLV - latest 30.09.2017) and clean data for the patients exist. After that the trial is terminated. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |