Breast Cancer Recurrent, HER2/Neu-negative Carcinoma of Breast, Hormone Receptor Positive Malignant Neoplasm of Breast
Conditions
Keywords
breast cancer, advanced, inoperable, metastatic, HER2/neu-negative, hormone receptor positive, HR+, female, postmenopausal
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.
Interventions
DRUGBevacizumab
administered as combined therapy with Capecitabine
DRUGCapecitabine
administered as combined therapy with Bevacizumab
DRUGEverolimus
administered as combined therapy with Exemestane
DRUGExemestane
administered as combined therapy with Everolimus
OTHERPatient questionaires
Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference
Sponsors
Arbeitsgemeinschaft fur Internistische Onkologie
Novartis Pharmaceuticals
iOMEDICO AG
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients' preference | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reasons for patients' preference | 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 |
| 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 | To compare patient reported treatment satisfaction as assessed by the treatment satisfaction questionnaire in first- and second 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 | 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 |
| Progression free survival rate | 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) |
| Safety and tolerability as measured by number of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities | 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) |
| Physicians' treatment preference | 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 |
| Progression free survival for first and second treatment phase | 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 |
| Overall survival | 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 |
| 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) | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | To explore relationship between QoL scores and patient preference (Exploratory objective) |
Countries
Germany
Outcome results
None listed