PROVIDENCE - Prospective Non-interventional Study (NIS) to Examine Patient-reported Outcomes and Real-world Clinical Data in Patients With HER2-positive or HER2-low Unresectable or Metastatic Breast Cancer Treated With Trastuzumab Deruxtecan (PROVIDENCE)

Prospective Non-interventional Study (NIS) to Examine Patient-reported Outcomes and Real-world Clinical Data in Patients With HER2-positive or HER2-low Unresectable or Metastatic Breast Cancer Treated With Trastuzumab Deruxtecan

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 unresectable or metastatic breast cancer (BC) and in patients with documented HER2-low unresectable or metastatic 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).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Breast Neoplasms; Neoplasm Metastasis

Detailed Description

Eligible participants will be those patients with documented HER2-positive unresectable or metastatic BC receiving T-DXd for 2L treatment or patients with documented HER2-low 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 cohort.

• Study Type: Observational
• Enrollment (Estimated): 800

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Germany
  • Amberg, Germany, 92224
    • Recruiting
    • Research Site
  • Ansbach, Germany, 91522
    • Recruiting
    • Research Site
  • Aschaffenburg, Germany, 63739
    • Recruiting
    • Research Site
  • Augsburg, Germany, 86150
    • Recruiting
    • Research Site
  • Bad Reichenhall, Germany, 83435
    • Recruiting
    • Research Site
  • Baden-Baden, Germany, 76532
    • Recruiting
    • Research Site
  • Beremerhaven, Germany, 27574
    • Recruiting
    • Research Site
  • Berlin, Germany, 10715
    • Recruiting
    • Research Site
  • Bonn, Germany, 53111
    • Recruiting
    • Research Site
  • Brandenburg an der Havel, Germany, 14770
    • Recruiting
    • Research Site
  • Bremen, Germany, 28209
    • Recruiting
    • Research Site
  • Donauwoerth, Germany, 86609
    • Recruiting
    • Research Site
  • Dortmund, Germany, 44137
    • Recruiting
    • Research Site
  • Eggenfelden, Germany, 84307
    • Recruiting
    • Research Site
  • Erfurt, Germany, 99085
    • Recruiting
    • Research Site
  • Freudenstadt, Germany, 72250
    • Recruiting
    • Research Site
  • Fuerstenwalde, Germany, 15517
    • Recruiting
    • Research Site
  • Gerlingen, Germany, 70839
    • Recruiting
    • Research Site
  • Giessen, Germany, 35392
    • Recruiting
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  • Hamburg, Germany, 21073
    • Recruiting
    • Research Site
  • Hannover, Germany, 30449
    • Recruiting
    • Research Site
  • Hannover, Germany, 30161
    • Recruiting
    • Research Site
  • Heidenheim, Germany, 89522
    • Recruiting
    • Research Site
  • Hildesheim, Germany, 31134
    • Recruiting
    • Research Site
  • Karlsruhe, Germany, 76135
    • Recruiting
    • Research Site
  • Kassel, Germany, 34117
    • Recruiting
    • Research Site
  • Kulmbach, Germany, 95326
    • Recruiting
    • Research Site
  • Landshut, Germany, 84036
    • Recruiting
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  • Leer, Germany, 26789
    • Recruiting
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  • Leipzig, Germany, 04103
    • Recruiting
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  • Loerrach, Germany, 79539
    • Recruiting
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  • Lüneburg, Germany, 21339
    • Recruiting
    • Research Site
  • Magdeburg, Germany, 39130
    • Recruiting
    • Research Site
  • Mainz, Germany, 55131
    • Recruiting
    • Research Site
  • Moenchengladbach, Germany, 41061
    • Recruiting
    • Research Site
  • Mutlangen, Germany, 73557
    • Recruiting
    • Research Site
  • Mühlhausen, Germany, 99974
    • Recruiting
    • Research Site
  • Neumarkt, Germany, 92318
    • Recruiting
    • Research Site
  • Oranienburg, Germany, 16515
    • Recruiting
    • Research Site
  • Potsdam, Germany, 14467
    • Recruiting
    • Research Site
  • Rosenheim, Germany, 83022
    • Recruiting
    • Research Site
  • Rotenburg (Wuemme), Germany, 27356
    • Recruiting
    • Research Site
  • Singen, Germany, 78224
    • Recruiting
    • Research Site
  • Solingen, Germany, 42653
    • Recruiting
    • Research Site
  • Stuttgart, Germany, 70199
    • Recruiting
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  • Torgau, Germany, 4860
    • Recruiting
    • Research Site
  • Troisdorf, Germany, 53840
    • Recruiting
    • Research Site
  • Weinheim, Germany, 69469
    • Recruiting
    • Research Site
  • Westerstede, Germany, 26655
    • Recruiting
    • Research Site
  • Wiesbaden, Germany, 65199
    • Recruiting
    • Research Site
  • Winnenden, Germany, 71364
    • Recruiting
    • Research Site
  • Zittau, Germany, 02763
    • Recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with documented Human epidermal growth factor receptor 2 (HER2)-positive unresectable or metastatic breast cancer (BC) and patients with documented HER2-low unresectable or metastatic BC receiving T-DXd in line with the applicable summary of product characteristics (SmPC) within routine clinical practice may participate in this NIS.

Description

Inclusion Criteria:

• Adults ≥ 18 years old
• Patients with pathologically documented breast cancer that:
• is unresectable or metastatic
• has confirmed HER2+ or HER2-low tumor status by local pathology
• was previously treated with one anti-HER2 directed therapy if the tumor is HER2+ 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.
• Has documented radiologic progression (during or after most recent treatment)
• Patient is eligible for T-DXd treatment in line with the specifications mentioned in the ENHERTU® SmPC and is scheduled for T-DXd as second line treatment if the tumor is HER2+ or scheduled for T-DXd treatment if the tumor is HER2 low*
• Patient is able to read and understand either German or English
• Signed written informed consent *The prescription of the medicinal products are clearly separated from the decision to include the patient in this NIS.

Exclusion Criteria:

• Known hypersensitivity to T-DXd or any of the excipients of the drug
• Pregnancy or breast feeding
• Current or planned participation in an interventional clinical trial
• Current or planned systemic treatment of any tumor other than unresectable or metastatic BC

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cohort 1; Cohort 1 containing patients with documented HER2-positive unresectable or metastatic BC receiving T-DXd for 2L treatment in line with the applicable summary of product characteristics (SmPC) within routine clinical practice.
Cohort 2; Cohort 2 containing patients with documented HER2-low unresectable or metastatic BC receiving T DXd treatment in line with the applicable summary of product characteristics (SmPC) within routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world Time To Next Treatment (rwTTNT1)	rwTTNT1 is defined as the time from T-DXd initiation to initiation of subsequent therapy	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HRQoL based on FACT-B questionnaire at 6 months after baseline	To evaluate patient-reported outcomes (PROs)/ health-related quality of life (HRQoL) based on FACT-B questionnaire at 6 months after baseline. The Functional Assessment of Cancer Therapy - Breast (FACT-B) is a 37-item instrument designed to measure five domains of HRQoL in breast cancer patients: Physical, social, emotional, functional well-being as well as a breast-cancer subscale (BCS). FACT-B will be collected electronically at time points synchronized with clinic visits during the study.	6 months
Change in HRQoL based on FACT-G questionnaire at 6 months after baseline	To evaluate patient-reported outcomes (PROs)/ health-related quality of life (HRQoL) based on FACT-G questionnaire at 6 months after baseline. The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire designed to measure four domains of HRQoL in cancer patients: Physical, social, emotional, and functional well-being. FACT-G will be collected electronically at time points synchronized with clinic visits during the study.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HRQoL based on EQ-5D questionnaire compared to baseline over time	Defined as changes in EQ-5D (subscale domains and VAS) at different timepoints compared to baseline. EQ-5D is a standardized instrument for use as a measure of patient-reported health outcomes (Euro-QoL). The 5 health-state dimensions in the EQ-5D-5L include: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 5-point scale from 1 (no problem) to 5 (unable to/extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale (EQ VAS) on which the participant rates his or her general state of health at the time of the assessment.	Patient questionnaires will be collected at time points synchronised with clinic visits during study, assessed up to 60 months
Real-world Progression-free Survival (rwPFS)	rwPFS is defined as time from T-DXd initiation to the date of the first source evidence for progression referenced by the clinician (e. g., radiology/ pathology report date) or the date of clinician note when no other corresponding evidence sources were documented) or death, whichever occurs first	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
Real-world Overall Survival (rwOS)	rwOS is defined as time from T-DXd initiation to date of death	From first dose of T-DXd until death of any cause, assessed up to 60 months
Real-world Time To Treatment Discontinuation (rwTTD)	rwTTD is defined as time from T-DXd initiation to discontinuation, or death	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
Real-world Time To Next Treatment 2	rwTTNT2 is defined as time from initiation of T-DXd treatment to initiation of second next treatment, or death	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
Real-world Progression-free Survival (rwPFS2)	rwPFS2 is defined as time from T-DXd initiation to the date of the first source evidence for the second progression referenced by the clinician (e. g., radiology/ pathology report date) or the date of clinician note when no other corresponding evidence sources were documented) or death, whichever occurs first	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
Change in HRQoL based on FACT-B questionnaire compared to baseline over time	Defined as changes in FACT-B (total score and subscale domains) at different timepoints compared to baseline. The Functional Assessment of Cancer Therapy - Breast (FACT-B) is a 37-item instrument designed to measure five domains of HRQoL in breast cancer patients: Physical, social, emotional, functional well-being as well as a breast-cancer subscale (BCS).	Patient questionnaires will be collected at time points synchronised with clinic visits during study, assessed up to 60 months
Real-world Overall Response Rate (rwORR)	rwORR is defined as percentage of patients having complete response or partial response as best response as determined by the investigator	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
Real-world Time to Treament Discontinuation 2 (rwTTD2)	rwTTD2 is defined as time from initiation T-DXd treatment to discontinuation of corresponding subsequent therapy, or death	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
Safety: Collection of Adverse Events (AE)	Safety evaluated based on type of Adverse Event (AE), intensity, causal relationship to treatment, duration, handling, outcome, and seriousness	during routine visits, up to 60 months
T-DXd dose modifications	To evaluate treatment modifications in patients treated with T-DXd in a real-world setting	during routine visits, up to 60 months
Description of DiGA user and non-user population	Age, Education, Family status, depressive mood, diagnostic testing, HR-status, Stage IV at initial diagnosis, localization of metastases, presence or history of (in) active brain metastases, previous therapies, subsequent therapies, center characteristics, DiGA usage	assessed up to 60 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2023
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: September 29, 2022
• First Submitted That Met QC Criteria: October 7, 2022
• First Posted (Actual): October 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Trastuzumab-Deruxtecan,; Human epidermal growth factor receptor 2 Positive Breast Cancer,; Human epidermal growth factor receptor 2 Low Breast Cancer,
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Neoplasms; Breast Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: D9673R00028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure