An Observational Study of Patients Receiving T-DXd for Treatment of HER2+, and HER2-low Unresectable and/or Metastatic Breast Cancer (DB RESPOND)

• ClinicalTrials.gov Identifier: NCT05592483
• Recruitment Status: Recruiting
• First Posted: October 24, 2022
• Last Update Posted: April 18, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: October 20, 2022
• First Posted Date: October 24, 2022
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: July 7, 2023
• Estimated Primary Completion Date: October 27, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2023)

• Real-World Time to Next Treatment (rwTTNT) [ Time Frame: From first dose of T-DXd until study discontinuation (approximately 3 years) ]
  Real-world time to next treatment will be evaluated. rwTTNT is defined as the length of time from date of first T-Dxd administration to the date the patient received an administration of their next systemic treatment regimen or to their date of death if there is a death prior to having another systemic treatment regimen.
• T-Dxd treatment patterns for HER2+ cohort [ Time Frame: Approximately 3 years ]
  Treatment patterns will be summarised using summary statistics.

Original Primary Outcome Measures (submitted: October 20, 2022)

• Real-World Time to Next Treatment (rwTTNT) [ Time Frame: From first dose of T-DXd until study discontinuation (approximately 3 years) ]
  Real-world time to next treatment will be evaluated. rwTTNT is defined as the length of time from date of first T-Dxd administration to the date the patient received an administration of their next systemic treatment regimen or to their date of death if there is a death prior to having another systemic treatment regimen.
• T-Dxd treatment patterns [ Time Frame: Approximately 3 years ]
  Treatment patterns will be summarised using summary statistics.

Current Secondary Outcome Measures (submitted: May 25, 2023)

• T-Dxd treatment patterns for HER2-low [ Time Frame: Approximately 3 years ]
  Treatment patterns will be summarised using summary statistics.
• Demographics and clinical charcteristics [ Time Frame: At Baseline (14 to 30 days prior to T-DXd initiation) ]
  Summary statistics will be used to describe the Demographics and clinical characteristics
• Number of patients with Physician reported Safety Events of Interest (SEIs) [ Time Frame: From first dose of T-DXd until End of T-DXd treatment (40 + 7 days after last T-DXd administration) ]
  The safety and tolerability of T-Dxd through the collection of physician-reported SEIs will be assessed.
• Number of patients provided prophylactic and reactive treatment for SEIs management [ Time Frame: From first dose of T-DXd until End of T-DXd treatment (40 + 7 days after last T-DXd administration) ]
  The management of SEIs will be characterized.
• Real-World Time to Discontinuation (rwTTD) [ Time Frame: From first dose of T-DXd until study discontinuation (approximately 3 years) ]
  Real-World Time to Discontinuation of T-DXd will be evaluated. rwTTD is defined as time from index date to the earliest date of T-DXd discontinuation, or death.
• Patient-reported overall side effect burden as measured by the Patient's Global Impression of Treatment Tolerability (PGI-TT) [ Time Frame: Approximately 3 years ]
  Patient-reported tolerability will be evaluated by PGI-TT. Single question asking patients how bothered they were by the side effects of their cancer treatment, ranging from Not at all to Very much.
• Symptomatic SEI as measured by selected items from National Cancer Institute Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) [ Time Frame: Approximately 3 years ]
  Patient-reported tolerability will be evaluated by selected items from the NCI PRO-CTCAE. The following items are selected: nausea, vomiting, bloating of the abdomen, shortness of breath, cough, heart palpitations, hair loss, and fatigue, tiredness or lack of energy.
• Daily Nausea and Vomiting symptom diary [ Time Frame: From first dose of T-DXd until 3 months ]
  Nausea and vomiting symptoms diary will be assessed based on severity, interference with appetite and usual activities.

Original Secondary Outcome Measures (submitted: October 20, 2022)

• Demographics and clinical charcteristics [ Time Frame: At Baseline (14 to 30 days prior to T-DXd initiation) ]
  Summary statistics will be used to describe the Demographics and clinical characteristics
• Number of patients with Physician reported Safety Events of Interest (SEIs) [ Time Frame: From first dose of T-DXd until End of T-DXd treatment (40 + 7 days after last T-DXd administration) ]
  The safety and tolerability of T-Dxd through the collection of physician-reported SEIs will be assessed.
• Number of patients provided prophylactic and reactive treatment for SEIs management [ Time Frame: From first dose of T-DXd until End of T-DXd treatment (40 + 7 days after last T-DXd administration) ]
  The management of SEIs will be characterized.
• Real-World Time to Discontinuation (rwTTD) [ Time Frame: From first dose of T-DXd until study discontinuation (approximately 3 years) ]
  Real-World Time to Discontinuation of T-DXd will be evaluated. rwTTD is defined as time from index date to the earliest date of T-DXd discontinuation, or death.
• Patient-reported overall side effect burden as measured by the Patient's Global Impression of Treatment Tolerability (PGI-TT) [ Time Frame: Approximately 3 years ]
  Patient-reported tolerability will be evaluated by PGI-TT. Single question asking patients how bothered they were by the side effects of their cancer treatment, ranging from Not at all to Very much.
• Symptomatic SEI as measured by selected items from National Cancer Institute Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE) [ Time Frame: Approximately 3 years ]
  Patient-reported tolerability will be evaluated by selected items from the NCI PRO-CTCAE. The following items are selected: nausea, vomiting, bloating of the abdomen, shortness of breath, cough, heart palpitations, hair loss, and fatigue, tiredness or lack of energy.
• Daily Nausea and Vomiting symptom diary [ Time Frame: From first dose of T-DXd until 3 months ]
  Nausea and vomiting symptoms diary will be assessed based on severity, interference with appetite and usual activities.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Observational Study of Patients Receiving T-DXd for Treatment of HER2+, and HER2-low Unresectable and/or Metastatic Breast Cancer
• Official Title: A Multi-center, Multi-country Prospective Observational Study of Patients Initiating T-DXd in the First or Second Treatment Line for HER2+, and HER2-low Unresectable and/or Metastatic Breast Cancer
• Brief Summary: This study will collect real-world clinical and patient reported outcomes (PRO) and diary data from eligible patients with documented Human Epidermal Growth Factor Receptor 2 (HER2+) [globally] or HER2-low [North America only] in routine clinical practice.

Detailed Description

This is a multi-center, observational prospective study that will characterize the demographic and clinical characteristics, treatment patterns, effectiveness, tolerability and its management, and patient experience of Trastuzumab Deruxtecan (T-DXd) in a real-world setting. This study is planned to be conducted in several countries and aims to enroll approximately 750 patients eligible patients with HER2+ unresectable and/or metastatic breast cancer (mBC) who has received a prior anti HER2 based regimen in the metastatic setting or in the neoadjuvant or adjuvant setting and has developed disease recurrence during or within 6 months of completing therapy. Approximately 250 eligible patients with HER2-low unresectable and/or mBC who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy will be enrolled into the study in North America only.

The planned duration of patient recruitment is approximately 18 months for HER2+ and approximately 12 months for HER2 low.

• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients with HER2+ and HER2-low unresectable and/or mBC who are prescribed T-DXd for 2L or earlier metastatic treatment per standard of care.
• Condition: Breast Cancer

Intervention

Other: None (Observational Study)

Not Applicable since observational study

Other Name: Observational study

Study Groups/Cohorts

• HER2+ Cohort
  Patients with HER2+ unresectable and/or mBC who are prescribed T-DXd and have received a prior anti-HER2 based regimen.
  Intervention: Other: None (Observational Study)
• HER2-low cohort
  Patients with HER2-low unresectable and/or mBC who are prescribed T-DXd and have received a prior chemotherapy.
  Intervention: Other: None (Observational Study)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 19, 2023): 1000
• Original Estimated Enrollment (submitted: October 20, 2022): 750
• Estimated Study Completion Date: October 27, 2026
• Estimated Primary Completion Date: October 27, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients ≥18 years of age at time of consent.
• Histological or cytological confirmed diagnosis of unresectable and/or mBC.
• Documented HER2 status via a validated method.
• Adult patients with unresectable or metastatic HER2+ breast cancer who have received a prior anti-HER2-based regimen in the metastatic setting or in the neoadjuvant or adjuvant setting and developed disease recurrence during or within 6 months of completing therapy.

Or

Adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

• Decision to newly initiate monotherapy T-DXd per standard of care.
• Capable of providing informed consent and completing questionnaires.

Exclusion Criteria:

• Pregnancy or breastfeeding.
• History of other primary malignancies in 2 years prior to unresectable and/or mBC diagnosis.
• Patients who at time of data collection for this study are participating in or have participated in an interventional study that remains blinded.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

• Listed Location Countries: Austria, Brazil, Canada, Israel, Italy, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT05592483
• Other Study ID Numbers: D9673R00025
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

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 requests 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.

• 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.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified 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.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AstraZeneca
• Verification Date: April 2024