Clinical trial NCT05573893: PROVIDENCE - Prospective Non-interventional Study (NIS) to Examine Patient-reported Outcomes and Real-world Clinical Data in Patients With HER2-positive, HER2-low or HER2-ultralow Unresectable or Metastatic Breast Cancer Treated With Trastuzumab Deruxtecan
Official title: Prospective Non-interventional Study (NIS) to Examine Patient-reported Outcomes and Real-world Clinical Data in Patients With HER2-positive, HER2-low or HER2-ultralow Unresectable or Metastatic Breast Cancer Treated With Trastuzumab Deruxtecan
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Neoplasms
Breast Cancer
Neoplasm Metastasis
Keywords: Trastuzumab-Deruxtecan,
Human epidermal growth factor receptor 2 Positive Breast Cancer,
Human epidermal growth factor receptor 2 Low Breast Cancer,
Human epidermal growth factor receptor 2 Ultralow Breast Cancer,
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2022-10-10
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with documented Human epidermal growth factor receptor 2 (HER2)-positive, HER2-low or HER2-ultralow unresectable or metastatic breast cancer (BC) receiving T-DXd in line with the applicable summary of product characteristics (SmPC) within routine clinical practice may participate in this NIS.

Brief summary: This is a prospective non-interventional, multicenter study observing patient reported outcomes as well as real-world efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with documented Human epidermal growth factor receptor 2 (HER2)-positive, HER2-low or HER2-ultralow unresectable or metastatic breast cancer (BC) receiving T-DXd in line with the applicable summary of product characteristics (SmPC) within routine clinical practice in Germany. In addition, patients will be informed about use of digital healthcare application (DiGA).

Detailed description: Eligible participants will be those patients with documented HER2-positive, HER2-low or HER2-ultralow unresectable or metastatic BC receiving T-DXd treatment in line with the applicable summary of product characteristics (SmPC) within routine clinical practice.

All diagnostic and treatment procedures including visit frequency are at the discretion of the treating physician and not defined by the protocol. T-DXd treatment is considered as a selection criteria. Patients will be informed about use of digital healthcare application (DiGA).

Approximately 800 eligible participants will be enrolled which includes 400 patients in the HER2-positive cohort and 400 patients in the HER2-low/ HER2-ultralow cohort.

Eligibility criteria: Inclusion Criteria:

1. Adults ≥ 18 years old
2. Patients (irrespective of sex and gender) with pathologically documented breast cancer that:

   * is unresectable or metastatic
   * has confirmed HER2+, HER2-low or HER2-ultralow tumor status by local pathology
   * was previously treated with one or more anti-HER2 directed therapy if the tumor is HER2+ OR
   * was previously treated with at least one endocrine therapy in the metastatic setting and is not considered suitable for endocrine therapy as the next line of treatment if the tumor is HR+, HER2-low or HER2-ultralow OR
   * was previously treated with prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy if the tumor is HER2-low.
3. Has documented radiologic progression (during or after most recent treatment)
4. Patient is eligible for T-DXd treatment in line with the specifications mentioned in the ENHERTU® SmPC and is scheduled for T-DXd treatment \*
5. Patient is able to read and understand either German or English
6. Signed written informed consent

   * The prescription of the medicinal product is clearly separated from the decision to include the patient in this NIS.

Exclusion Criteria:

1. Start of T-DXd treatment for more than 30 days before enrolment (eCRF registration date)
2. Known hypersensitivity to T-DXd or any of the excipients of the drug
3. Pregnancy or breast feeding
4. Current or planned participation in an interventional clinical trial
5. Current or planned systemic treatment of any tumor other than unresectable or metastatic BC

Patients who have never received any T-DXd dose will be discontinued from the study and will be considered as a late screening failure, no further documentation besides reason and date of discontinuation is needed.

Primary outcomes:
measure: Real-world Time To Next Treatment (rwTTNT1)
timeFrame: From first dose of T-DXd until initiation of subsequent therapy or death of any cause, whichever came first, assessed up to 60 months
Secondary outcomes:
measure: Change in HRQoL based on FACT-B questionnaire at 6 months after baseline
timeFrame: 6 months
measure: Change in HRQoL based on FACT-G questionnaire at 6 months after baseline
timeFrame: 6 months
Other outcomes:
measure: Change in HRQoL based on FACT-B questionnaire compared to baseline over time
timeFrame: Patient questionnaires will be collected at time points synchronised with clinic visits during study, assessed up to 60 months
measure: Change in HRQoL based on EQ-5D questionnaire compared to baseline over time
timeFrame: Patient questionnaires will be collected at time points synchronised with clinic visits during study, assessed up to 60 months
measure: Real-world Overall Response Rate (rwORR)
timeFrame: From first dose of T-DXd until end of T-DXd treatment or death of any cause, whichever came first (investigator-assessed according to clinical routine), assessed up to 60 months
measure: Real-world Progression-free Survival (rwPFS)
timeFrame: From first dose of T-DXd until disease progression (investigator-assessed according to clinical routine) or death of any cause, whichever came first, assessed up to 60 months
measure: Real-world Overall Survival (rwOS)
timeFrame: From first dose of T-DXd until death of any cause, assessed up to 60 months
measure: Real-world Time To Treatment Discontinuation (rwTTD)
timeFrame: From first dose of T-DXd until discontinuation of T-DXd treatment therapy or death of any cause, whichever came first, assessed up to 60 months
measure: Real-world Time To Next Treatment 2 (rwTTNT2)
timeFrame: From first dose of T-DXd until initiation of second subsequent therapy or death of any cause, whichever came first, assessed up to 60 months
measure: Real-world Time to Treament Discontinuation 2 (rwTTD2)
timeFrame: From first dose of T-DXd until discontinuation of corresponding subsequent therapy or death of any cause, whichever came first, assessed up to 60 months
measure: Real-world Progression-free Survival (rwPFS2)
timeFrame: From first dose of T-DXd until second disease progression (investigator-assessed according to clinical routine) or death of any cause, whichever came first, assessed up to 60 months
measure: Safety: Collection of Adverse Events (AE)
timeFrame: during routine visits, up to 60 months
measure: T-DXd dose modifications
timeFrame: during routine visits, up to 60 months
measure: Description of DiGA user and non-user population
timeFrame: assessed up to 60 months
Locations:
city: Amberg
country: Germany
facility: Research Site
city: Ansbach
country: Germany
facility: Research Site
city: Apolda
country: Germany
facility: Research Site
city: Aschaffenburg
country: Germany
facility: Research Site
city: Augsburg
country: Germany
facility: Research Site
city: Bad Reichenhall
country: Germany
facility: Research Site
city: Baden-Baden
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bielefeld
country: Germany
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Brandenburg an der Havel
country: Germany
facility: Research Site
city: Braunschweig
country: Germany
facility: Research Site
city: Bremen
country: Germany
facility: Research Site
city: Bremerhaven
country: Germany
facility: Research Site
city: Coburg
country: Germany
facility: Research Site
city: Dessau
country: Germany
facility: Research Site
city: Donauwoerth
country: Germany
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Duesseldorf
country: Germany
facility: Research Site
city: Eggenfelden
country: Germany
facility: Research Site
city: Erfurt
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Filderstadt - Bonlanden
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Freudenstadt
country: Germany
facility: Research Site
city: Fuerstenfeldbruck
country: Germany
facility: Research Site
city: Fuerstenwalde
country: Germany
facility: Research Site
city: Gerlingen
country: Germany
facility: Research Site
city: Giessen
country: Germany
facility: Research Site
city: Halle (Saale)
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Heidenheim
country: Germany
facility: Research Site
city: Heilbronn
country: Germany
facility: Research Site
city: Hildesheim
country: Germany
facility: Research Site
city: Homburg/Saar
country: Germany
facility: Research Site
city: Jena
country: Germany
facility: Research Site
city: Karlsruhe
country: Germany
facility: Research Site
city: Kassel
country: Germany
facility: Research Site
city: Kassel
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Kulmbach
country: Germany
facility: Research Site
city: Landshut
country: Germany
facility: Research Site
city: Leer
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Loerrach
country: Germany
facility: Research Site
city: Luebeck
country: Germany
facility: Research Site
city: Lueneburg
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: Moenchengladbach
country: Germany
facility: Research Site
city: Muehlhausen
country: Germany
facility: Research Site
city: Muenchen
country: Germany
facility: Research Site
city: Muenchen
country: Germany
facility: Research Site
city: Mutlangen
country: Germany
facility: Research Site
city: Neumarkt
country: Germany
facility: Research Site
city: Neustadt Am Ruebenberge
country: Germany
facility: Research Site
city: Nordhausen
country: Germany
facility: Research Site
city: Nurnberg
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Oranienburg
country: Germany
facility: Research Site
city: Potsdam
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Rosenheim
country: Germany
facility: Research Site
city: Rotenburg (Wuemme)
country: Germany
facility: Research Site
city: Saalfeld (Saale)
country: Germany
facility: Research Site
city: Saarbruecken
country: Germany
facility: Research Site
city: Salzwedel
country: Germany
facility: Research Site
city: Schwaebisch-Hall
country: Germany
facility: Research Site
city: Singen
country: Germany
facility: Research Site
city: Solingen
country: Germany
facility: Research Site
city: Stade
country: Germany
facility: Research Site
city: Stuttgart
country: Germany
facility: Research Site
city: Torgau
country: Germany
facility: Research Site
city: Troisdorf
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Weiden
country: Germany
facility: Research Site
city: Weinheim
country: Germany
facility: Research Site
city: Weissenfels
country: Germany
facility: Research Site
city: Westerstede
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Winnenden
country: Germany
facility: Research Site
city: Wuerzburg
country: Germany
facility: Research Site
city: Wuppertal
country: Germany
facility: Research Site
city: Zittau
country: Germany
facility: Research Site
Study officials:
References: