Evaluation of the Medidux™ Digital Health Application in Patients With HER2-positive Breast Cancer During Chemotherapy in Combination With HER2-targeted Therapy or Antibody-drug Conjugate Therapy.

Study Overview
=================
Brief Summary
-----------------
Multicenter, prospective, randomised and controlled study to evaluate the medidux™ app during an observation period of 12 weeks (maximum 16 weeks in case of shifts in the initially planned therapy).

Detailed Description
-----------------
The PRO2 study is being conducted by palleos healthcare GmbH, the sponsor of the study, with the participation of an expected 585 patients at 40 study sites in Germany and 10 study sites in the German-speaking part of Switzerland with the aim of investigating the medical benefit of the smartphone application medidux™ (app) with regard to the occurrence of side effects in breast cancer therapy. Furthermore, the potential impact on the application of the chemotherapy or antibody-drug conjugate, respectively, the number of unplanned doctor visits, as well as hospitalizations and how often the app is used will be investigated. The app was developed by mobile Health AG and is intended to accompany therapy. It is an approved CE-marked medical device that will be used in the study within the intended purpose. Study participants can use the app to document symptoms and well-being, as well as vital signs (e.g., blood pressure), and complete a test that can be used to assess mental performance. The entries can be viewed by the study physician through the medidux™ web application. The study participants can refer to the entries during the treatment visit to explain the course of therapy and perceived symptoms. As part of the study, use of the app will be compared to the normal treatment routine (without the app). A randomization process will determine whether study participants receive the app. The probability of receiving the app is 50%. If study participants receive the app, it can be used after installation on the personal smartphone. The approximately 12- to a maximum of 16-week observation period begins with the regular breast cancer therapy. The specific treatment of the breast cancer is not interfered with during the study, i.e. the administration of the therapy itself is carried out in the same way as it would be without the app.

Official Title
-----------------
Evaluation of the Medidux™ Digital Health Application in Patients With HER2-positive Breast Cancer During Chemotherapy in Combination With HER2-targeted Therapy (Including Tyrosine Kinase Inhibitors [TKI]) or an Antibody-drug Conjugate Therapy: a Multicenter Randomized Controlled Trial.

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Device: medidux™ app


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with signed informed consent. Female and male patients, age at diagnosis 18 years and older. Patients with HER2-positive breast carcinoma* (confirmed by a local pathologist). Patients with breast carcinoma with positive or negative hormone receptor status. Patients prior to initiation of neoadjuvant, adjuvant or palliative chemotherapy** in combination with HER2-targeted therapy (including tyrosine kinase inhibitors [TKI]) or an antibody-drug conjugate therapy. ECOG performance Status ≤ 1. Sufficient command of the German language as assessed by the investigator. Presence of a personal smartphone with iOS or Android system. The operating system must be updated to the latest, second or third most recent major version and the medidux™ app must be installed prior to the start of the first treatment cycle. * HER2-positive in the context of the study defined as eligible for an approved HER2-targeted therapy, i.e., in addition to immunohistochemistry (IHC) scores of 3+ and 2+ with positive results of in-situ hybridization (ISH+), also according to new standard HER2 low (IHC 1+ and 2+ with simultaneous negative result of in-situ-hybridization (ISH-)) ** Patients receiving chemotherapy in combination with HER2-targeted therapy as part of a (neo)adjuvant sequence therapy (e.g. as second part after previous EC therapy) may be included. Accordingly, the PRO2 study will not start until patients begin combination of chemotherapy and HER2-targeted therapy. Exclusion Criteria: Patients for whom it is questionable whether they will follow the study protocol, e.g., due to psychological problems or their private life situation. Patients with insufficient knowledge about the use of smartphones. Patients at the start of therapy with an ECOG performance status ≥ 2. Patients who have already used the medidux™ app or its predecessor consilium care™ before admission to the study. Patients with breast carcinoma who are to be treated exclusively with HER2-targeted antibody monotherapy or TKI-therapy without simultaneous chemotherapy. The sole administration of antibody-drug conjugates alone is permitted/prescribed by the SmPC. Simultaneous participation in an interventional clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Experimental group is using the medidux™ app | Device: medidux™ app<br>* Use of the regular medidux™ application for 12 (maximum 16) weeks<br>|
| No Intervention: Arm B<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse events (AEs) (CTCAE severity >2) and serious AEs (SAE) within the observation period. | As the primary endpoint, the occurrence of adverse events, either of type SAE or of type AE with CTCAE severity >2, with a start date within the observation period will be measured for each patient. In the following, these events are referenced as high-grade AEs (HAE). The parameters included in the primary endpoint analysis are recorded by the investigator during regular study visits within 12 weeks. The observation period can, however, be extended to the period required for the completion of the initially planned therapy due to shifts in therapy; the maximum observation period is limited to 16 weeks. Adverse events are mapped to the hierarchy and thesaurus terms of the Medical Dictionary for Regulatory Activities (MedDRA, latest version). Severity will be determined according to NCI CTCAE v5.0. In addition to the assessment by the investigators and the medical monitor, the HAEs will be assessed by a blinded medical expert (Adjudicator) and a classification is made independently. | From the day of randomization until Day 84; maximum observation period is 16 weeks (112 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AE) occurring in the observation period recorded and assessed by the investigator during the scheduled study visits. | Adverse events (AE) occurring in the observation period recorded and assessed by the investigator during the scheduled study visits. Events classified as hair loss (alopecia) are excluded from the analysis as they cannot be influenced a priori by the medidux™ app but may be subject to a technological center bias due to the availability of cold caps, which cannot be controlled within the scope of the study. Adverse events are mapped to hierarchy and thesaurus terms of the Medical Dictionary for Regulatory Activities (MedDRA, latest version). Severity is determined according to NCI CTCAE v5.0. | From the day of randomization until Day 84; maximum observation period is 16 weeks (112 days) | 
| Serious adverse events (SAEs) | Serious adverse events (SAEs), defined as a subset of the adverse events defined under Outcome 2 that are classified as serious. | From the day of randomization until Day 84; maximum observation period is 16 weeks (112 days) | 
| Number of patients with at least one documented chemotherapy (CTX) respectively antibody-drug conjugate dose reduction. | Number of patients with at least one documented chemotherapy (CTX) respectively antibody-drug conjugate dose reduction. | From the day of randomization until Day 84; maximum observation period is 16 weeks (112 days) | 
| CTX respectively antibody-drug conjugate adherence | CTX respectively antibody-drug conjugate adherence defined as the percentage of cumulative chemotherapy respectively antibody-drug conjugate dose actually received relative to the planned cumulative dose. | From the day of randomization until Day 84; maximum observation period is 16 weeks (112 days) | 
| Number of treatment-associated unplanned emergency consultations | Unplanned emergency consultations are defined as emergency-related consultations outside of planned treatment or follow-up visits to the treatment center or the investigator, as well as unplanned visits to other physicians or emergency services. | From the day of randomization until Day 84; maximum observation period is 16 weeks (112 days) | 
| Number of hospitalisations | Number of hospitalisations defined as inpatient admission at the center or at another medical facility because of an (S)AE | From the day of randomization until Day 84; maximum observation period is 16 weeks (112 days) | 
| Number and severity of symptoms recorded by medidux™ in the experimental arm. | Number and severity of symptoms recorded by medidux™ (for ePRO modified NCI CTCAE 4.0 subset of 106 items for cancer) in the experimental arm. ePRO symptoms can be continuously documented via the app by the patient. | From the day of randomization until Day 84; maximum observation period is 16 weeks (112 days) | 
| Adherence | Adherence defined for the experimental arm as the percentage of days in the observation period on which any form of use of the medidux™ app took place. | From the day of randomization until Day 84; maximum observation period is 16 weeks (112 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
app, PRO2, medidux, ePro, palleos, xlife science, mobile Health AG, mobile Health, medical device, palleos healthcare