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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- iOMEDICO AG
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- Patients' preference
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Arm A
Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase)
Dosing (treatment cycle: 21days):
- 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)
- 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)
干预措施: Bevacizumab (Drug)
Arm A
Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase)
Dosing (treatment cycle: 21days):
- 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)
- 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)
干预措施: Capecitabine (Drug)
Arm A
Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase)
Dosing (treatment cycle: 21days):
- 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)
- 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)
干预措施: Everolimus (Drug)
Arm A
Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase)
Dosing (treatment cycle: 21days):
- 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)
- 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)
干预措施: Exemestane (Drug)
Arm A
Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase)
Dosing (treatment cycle: 21days):
- 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)
- 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)
干预措施: Patient questionaires (Other)
Arm B
Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase)
Dosing (treatment cycle: 21days):
- Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet
- 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)
干预措施: Bevacizumab (Drug)
Arm B
Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase)
Dosing (treatment cycle: 21days):
- Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet
- 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)
干预措施: Capecitabine (Drug)
Arm B
Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase)
Dosing (treatment cycle: 21days):
- Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet
- 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)
干预措施: Everolimus (Drug)
Arm B
Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase)
Dosing (treatment cycle: 21days):
- Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet
- 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)
干预措施: Exemestane (Drug)
Arm B
Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase)
Dosing (treatment cycle: 21days):
- Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet
- 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)
干预措施: Patient questionaires (Other)
结局指标
主要结局
Patients' preference
时间窗: 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.
次要结局
- 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)
- 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)
- 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))
- Overall survival(Participants will be followed until death (expected median of 24 months))
- 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))
- Progression free survival rate(After 12 weeks of first and second treatment phase)
- Reasons for patients' preference(After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation)
- 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)
- Physicians' treatment preference(After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation)