Impact of eHealth-support on Quality of Life in metastatic breast cancer patients treated with Palbociclib and endocrine therapy

INTERVENTION: Trade Name: IBRANCE 125mg Hartkapseln Pharmaceutical Form: Capsule, hard INN or Proposed INN: PALBOCICLIB CAS Number: 571190‐30‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 125‐ Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: Fulvestrant CAS Number: 129453‐61‐8 Other descriptive name: FULVESTRANT Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50‐ Pharmaceutical Form: Coated tablet INN or Proposed INN: Anastrozole CAS Number: 120511‐73‐1 Other descriptive name: ANASTROZOLE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Pharmaceutical Form: Coated tablet INN or Proposed INN: LETROZOLE CAS Number: 112809‐51‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2,5‐ Pharmaceutical Form: Coated tablet INN or Proposed INN: Exemestan CAS Number: 107868‐30‐4 Other descriptive name: EXEMESTANE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ CONDITION: advanced and or metastatic breast cancer Therapeutic area: Diseases [C] ‐ Cancer [C04] INCLUSION CRITERIA: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Women 18 years of age or older, who are either: • Post‐menopausal, as defined by at least one of the following criteria: ‐ Age = 60 years; ‐ Age <60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; or serum estradiol and FSH level within the laboratory’s reference range for post‐menopausal females; ‐ Documented bilateral oophorectomy; ‐ Medically confirmed ovarian failure. OR ‐ Pre/peri‐menopausal, i.e., not meeting the criteria for being postmenopausal. ‐ Pre/peri‐meopausal women can be enrolled if amenable to be treated with a LHRH‐agonist. Patients should be treated with a LHRH‐agonist. 2. Patients have to have metastatic disease or locally advanced (non‐operable) breast cancer disease. 3. Patients who are appropriate candidates for aromatas PRIMARY OUTCOME: Main Objective: To demonstrate superiority w.r.t. time to deterioration (TTD) of quality of life for patients with eHealth‐based high density observation using CANKADO (CANKADO active) versus eHealth‐based static observation on site (CANKADO inform). Primary end point(s): • TTD (time to deterioration) with respect to DQoL (deterioration of quality of life as a 10‐point drop on FACT‐G) ; ; Time to deterioration (TTD) with respect to DQoL is defined as the difference between time of treatment allocation (randomization) and time of DQoL. Patients not meeting deterioration criteria are to be censored at death or a maximum of 48 months of follow‐up after treatment allocation. ; ; The event “deterioration of quality of life” (DQoL) is defined as any decrease of 10 or more points from baseline in QoL as assessed using the FACT‐G scale, unless a recovery is achieved in the subsequent assessment. A recovery is defined as a QoL score no worse than 9 points below baseline. If data of the subsequent visit is missing, a decrease of 10 or more points will be considered as event.; The definition of DQoL as a 10‐point decrease on the FACT‐G scale is based on Cella et al. (2002) and corresponds to a mean change from baseline in a subgroup of various cancer patients who classified the change as “minimally worse” according to a global rating of change (GRC) scale administered immediately after the FACT‐G. ; Note that Eton et al. (2004) also suggested a 5‐6 points change on FACT‐G as minimally important difference (MID) in metastatic breast cancer patients. It is expected that the conservative choice of a 10‐point decrease will be more robust against less meaningful fluctuations of the QoL measurement time series in the context of the precycle trial.; A definition of DQoL in terms of MID (5‐point decrease on FACT‐G) will be used for sensitivity analyses in a dedicated secondary objective. Secondary Objective: i. Sensitivity Analysis: To compare TTD DQoL between the two treatment arms in terms of DQoL as minimally important difference (5‐point drop on FACT‐G).; ii. To demonstrate that an eHealth‐based high density observation using CANKADO does not have a negative impact on clinical outcome (PFS, OS).; iii. To analyze the effect of patient reported outcome (PRO; data of daily drug intake behavior, global health status, quality of life) w.r.t. clinical outcome (PFS, OS) and DQoL; Timepoint(s) of evaluation of this end point: Patients in Arm A have to complete the EQ‐VAS scale and document their drug intake daily. Additionally a FACT‐B questionnaire can be triggered if the reported health status on the EQ‐VAS scale changes by 10 or more score points in comparison to the mean value of the last three days or over a period of seven days compared to the mean value of seven days before.; Patients in Arm B will be provided with FACT‐B questionnaire on‐site and can document the daily drug intake.; ; For both study arms patients have to fill in the FACT‐B questionnaire on‐site on day 1 of every planned study visit during active treatment phase. In the event of dose interruptions when patients must come on‐site more often than for the scheduled visits they may also be requested to complete the FACT‐B questionnaire. SECONDARY OUTCOME: Secondary end point(s): Secondary Objectives:; i. Sensitivity Analysis: To compare TTD DQoL between the two treatment arms in terms of DQoL as minimally important difference (5‐point drop on FACT‐G).; ii. To demonstrate that an eHealth‐based high density observation using CANKADO does not have a negative impact on clinical outcome (PFS, OS).; iii. To analyze the effect of patient reported outcome (PRO; data of daily drug intake behavior, global health status, quality of life) w.r.t. clinical outcome (PFS, OS) and DQoL.; ; Endpoints:; • PFS (progression‐free survival); • OS (overall survival); • DQoL (deterioration of quality of life); ; Progression‐free survival (PFS) is considered to be the main clinical outcome and is defined as the time between treatment allocation and either first documentation of objective progression of disease (PD, as assessed by Investigator) or death due to any cause in absence of PD. ; ; Overall survival is defined as the time between treatment allocation and death due to any cause. ; ; The event “deterioration of quality of life” (DQoL) is defined as any decrease of 10 or more points from baseline in QoL as assessed using the FACT‐G scale, unless a recovery is achieved in the subsequent assessment. A recovery is defined as a QoL score no worse than 9 points below baseline. If data of the subsequent visit is missing, a decrease of 10 or more points will be considered as event.; The definition of DQoL as a 10‐point decrease on the FACT‐G scale is based on Cella et al. (2002) and corresponds to a mean change from baseline in a subgroup of various cancer patients who classified the change as “minimally worse” according to a global rating of change (GRC) scale administered immediately after the FACT‐G. ; Note that Eton et al. (2004) also suggested a 5‐6 points change on FACT‐G as minimally important difference (MID) in metastatic breast cancer patients. It is expected that the conservative choice of a 10‐point decrease will be more robust against less meaningful fluctuations of the QoL measurement time series in the context of the precycle trial.; A definition of DQoL in terms of MID (5‐point decrease on FACT‐G) will be used for sensitivity analyses in a dedicated secondary objective.; Timepoint(s) of evaluation of this end point: Outcome Measure(s) and Timepoint(s): ; ‐ PFS (progression‐free survival): every 3 months as long as under study treatment ; ‐ OS (overall survival): every 12 months under study treatment and during follow up phase; ‐ DQoL (deterioration of quality of life): every 28 days as long sa under study treatment;