A Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in Advance Breast Cancer. (BOLERO-6)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in the Treatment of Postmenopausal Women With ER+Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Prior Letrozole or Anastrozole.|
- Progression Free Survival (PFS) [ Time Frame: 28 months after first patient randomized or once 150 PFS have occurred ]Once 150 PFS events have occured (determined by local assessment). To estimate the hazard ratio of PFS for everolimus plus exemestane versus everolimus alone in postmenopausal women with ER positive, HER2 negative, advanced breast cancer after recurrence or progression on letrozole or anastrozole.
- Overall Survival [ Time Frame: Every 3 months following the end of study visit until 2015 (up to 3 years) ]To evaluate the treatment groups with respect to Overall Survival. End of study visit is defined as time when progression of disease recorded or death whichever comes first.
- Overall response rate [ Time Frame: From the date of first dose of study medication until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately for 28 months ]Overall response rate (ORR) based on the local radiologist/investigator's tumor assessment (RECIST 1.1)
- Clinical benefit rate (CBR) [ Time Frame: From the date of first dose of study medication until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 28 months ]Clinical Benefit Rate is defined as the proportion of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD) with duration of 24 weeks or longer.
- Changes in ECOG (Eastern Cooperative Oncology Group) performance status [ Time Frame: Baseline, Day 1, every 6 weeks for approximately 8 months ]The ECOG performance status scale (1-5) allows patients to be classified as to their functional impairment, ECOG performance status will be compared to baseline ECOG performance classification.
- Change in quality of life scores over time: EORTC (QLQ-C30)/EORTC module (BR23) [ Time Frame: Baseline, every 6 weeks for approximately 8 months ]
- Time to quality of life (QoL)deterioration : TSQM score [ Time Frame: Baseline, week 3,6, 12 for approximately 8 months ]
- Safety: Incidence of Adverse Event(s) [ Time Frame: every study visit for approximately 8 months ]
- Safety: Incidence of Serious Adverse Events [ Time Frame: every study visit for approximately 8 months ]
- Safety: changes in vital signs when compared to baseline vital signs [ Time Frame: baseline, every study visit for approximately 8 months ]
- Safety: changes in laboratory values compared to laboratory values obtained at the baseline visit [ Time Frame: baseline, every study visit for approximately 8 months ]
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||October 2017|
|Estimated Primary Completion Date:||October 2017 (Final data collection date for primary outcome measure)|
Experimental: Capecitabine Monotherapy
100 patients will be randomized to the Capecitabine monotherapy arm (1250mg/m2 twice daily) orally for two weeks, followed by a one week rest period in 3-weeks cycles.
Capecitabine, for oral use 1250 mg/m2 twice daily for 2 weeks followed by one week rest (3-week cycle). Capecitabine will be locally supplied by the Investigator.
Other Name: Capecitabine monotherapy
Experimental: Everolimus Monotherapy
100 patients will be randomized to this arm and will received Everolimus (10mg daily).
Everolimus will be centrally dispensed via IWRS. Everolimus will be taken as oral tablets for oral use 10 mg (2 × 5 mg) daily.
Other Name: RAD001
Active Comparator: Everolimus with Exemestane
100 patients will be randomized to the control arm of this study, everolimus (10mg daily) with exemestane (25mg daily).
Exemestane tablets of 25 mg will be taken orally once per day. Dose modifications in the management of adverse events is allowed.
Other Name: Control Arm
This is a three-arm, randomized, open label, multi-center phase II study investigating the combination of everolimus (10mg daily) with exemestane (25mg daily) versus everolimus (10mg daily) versus capecitabine (1250mg/m2 twice daily for 14 days, 3-week cycle) in patients with estrogen-receptor positive, HER2 negative, advanced breast cancer after recurrence or progression on letrozole or anastrozole. The reference therapy (control arm) used in the course of this trial is the combination arm of everolimus plus exemestane. The investigational therapies in the context of this study are everolimus monotherapy and capecitabine monotherapy. All treatments will be taken orally until disease progression, intolerable toxicity or withdrawal of patient's informed consent. Patients will be randomly assigned with equal allocation to one of the treatment arms:
- Exemestane (25mg daily) in combination with everolimus (10mg daily)
- Everolimus (10mg daily)
- Capecitabine (1250mg/m2 twice daily) orally for two weeks, followed by a one week rest period in 3-weeks cycles.
Treatment assignment will be stratified by the presence of visceral disease (yes vs. no). Visceral refers to lung, liver, heart, ovary, spleen, kidney, adrenal gland, malignant pleural or pericardial effusion or malignant ascites.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01783444
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|