Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06595563
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-04
Brief Title:
HER2 Molecular Imaging with 89Zr-trastuzumab PETCT As a Predictive Biomarker for Antibody-drug Conjugate Sequencing in Patients with Advanced HER2-positive Breast Cancer
Sponsor:
None
Organization:
None
Study Overview
Official Title:
HER2 Molecular Imaging with 89Zr-trastuzumab PETCT As a Predictive Biomarker for Antibody-drug Conjugate Sequencing in Patients with Advanced HER2-positive Breast Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ZEPHIR-02
Brief Summary:
ZEPHIR-02 is a multicentre open-label phase II study that will enroll subjects with HER2-positive advancedmetastatic breast cancer mBC who have experienced disease progression under trastuzumab deruxtecan T-DXd in the metastatic setting
All subjects will undergo baseline biopsy blood collection FDG-PETCT and 89Zr-trastuzumab PETCT HER2-PETCT and will be classified as HER2-PETCT positive or negative as previously described in the ZEPHIR trial Subjects classified as positive cohort A will receive T-DM1 as monotherapy IV 36mgkg every 3 weeks 21 days - 3 days until disease progression unacceptable toxicity or request of the subject to withdraw from the study Early FDG PETCT will be performed before cycle 2 of T-DM1 to assess the response to the treatment Routine tumour assessments will be performed with FDG-PETCT until efficacy follow-up is completed After 2 years of treatment with T-DM1 received by the subject physician can consider to space the cycles up to 6 weeks
Subjects classified as HER2-PETCT negative cohort B will receive treatment of physicians choice as per the best local clinical practice
The study also includes mandatory translational procedures ie collection of tumour biopsy during pre-treatment period and blood samples at pre-specified time points for exploratory molecular analyses
All subjects will undergo baseline biopsy blood collection FDG-PETCT and 89Zr-trastuzumab PETCT HER2-PETCT and will be classified as HER2-PETCT positive or negative as previously described in the ZEPHIR trial Subjects classified as positive cohort A will receive T-DM1 as monotherapy IV 36mgkg every 3 weeks 21 days - 3 days until disease progression unacceptable toxicity or request of the subject to withdraw from the study Early FDG PETCT will be performed before cycle 2 of T-DM1 to assess the response to the treatment Routine tumour assessments will be performed with FDG-PETCT until efficacy follow-up is completed After 2 years of treatment with T-DM1 received by the subject physician can consider to space the cycles up to 6 weeks
Subjects classified as HER2-PETCT negative cohort B will receive treatment of physicians choice as per the best local clinical practice
The study also includes mandatory translational procedures ie collection of tumour biopsy during pre-treatment period and blood samples at pre-specified time points for exploratory molecular analyses
Detailed Description:
ZEPHIR-02 is a multicentre open-label phase II study that will enroll subjects with HER2-positive advancedmetastatic breast cancer mBC who have experienced disease progression under trastuzumab deruxtecan T-DXd in the metastatic setting
All subjects will undergo baseline biopsy blood collection FDG-PETCT and 89Zr-trastuzumab PETCT HER2-PETCT and will be classified as HER2-PETCT positive or negative as previously described in the ZEPHIR trial Focusing on a central visual patient-based classification that captures the entire disease burden a side-by-side display will be used comparing baseline FDG-PETCT which identifies all FDG-positive metastases regardless of their HER2-imaging status and HER2-PETCT Subjects will be categorized into two HER2-PETCT patterns positive vs negative based on proportion of FDG-avid tumour load with significant 89Zr-trastuzumab uptake Lesion uptake will be considered significantpertinent if it is visually higher than the local background
HER2-PETCT positive pattern The entire or majority of the tumour load shows significant tracer uptake
HER2-PETCT negative pattern The dominant part or all of the tumour load lacks significant tracer uptake
Subjects classified as positive cohort A will receive T-DM1 as monotherapy IV 36mgkg every 3 weeks 21 days - 3 days until disease progression unacceptable toxicity or request of the subject to withdraw from the study FDG-PETCT will be performed before cycle 2 of T-DM1 for early assessment of response and then again before cycle 4 At the early FDG-PETCT assessment before cycle 2 response assessment will be done using a cut-off of 15 based on the CONSIST criteria Subjects who demonstrate a partial or complete response responders and will continue treatment with T-DM1 Subjects who exhibit stable disease or disease progression non-responders will discontinue study treatment and enter the survival follow-up period For responders subsequent metabolic evaluations will be performed every 3 months with FDG-PETCT Treatment response will be assessed according to metabolic response For these subjects blood samples will be obtained at all metabolic reassessments mandatory
The subjects with HER2 PETCT classified as negative cohort B will receive treatment of physicians choice TPC as per the best local clinical practice Subsequent treatment will be collected and the subject will enter survival follow-up
All enrolled subjects will undergo a mandatory biopsy during the pre-treatment period Of note results of DNA sequencing on the biopsy will be communicated to the treating oncologist to potentially inform post progression therapy
All subjects will undergo baseline biopsy blood collection FDG-PETCT and 89Zr-trastuzumab PETCT HER2-PETCT and will be classified as HER2-PETCT positive or negative as previously described in the ZEPHIR trial Focusing on a central visual patient-based classification that captures the entire disease burden a side-by-side display will be used comparing baseline FDG-PETCT which identifies all FDG-positive metastases regardless of their HER2-imaging status and HER2-PETCT Subjects will be categorized into two HER2-PETCT patterns positive vs negative based on proportion of FDG-avid tumour load with significant 89Zr-trastuzumab uptake Lesion uptake will be considered significantpertinent if it is visually higher than the local background
HER2-PETCT positive pattern The entire or majority of the tumour load shows significant tracer uptake
HER2-PETCT negative pattern The dominant part or all of the tumour load lacks significant tracer uptake
Subjects classified as positive cohort A will receive T-DM1 as monotherapy IV 36mgkg every 3 weeks 21 days - 3 days until disease progression unacceptable toxicity or request of the subject to withdraw from the study FDG-PETCT will be performed before cycle 2 of T-DM1 for early assessment of response and then again before cycle 4 At the early FDG-PETCT assessment before cycle 2 response assessment will be done using a cut-off of 15 based on the CONSIST criteria Subjects who demonstrate a partial or complete response responders and will continue treatment with T-DM1 Subjects who exhibit stable disease or disease progression non-responders will discontinue study treatment and enter the survival follow-up period For responders subsequent metabolic evaluations will be performed every 3 months with FDG-PETCT Treatment response will be assessed according to metabolic response For these subjects blood samples will be obtained at all metabolic reassessments mandatory
The subjects with HER2 PETCT classified as negative cohort B will receive treatment of physicians choice TPC as per the best local clinical practice Subsequent treatment will be collected and the subject will enter survival follow-up
All enrolled subjects will undergo a mandatory biopsy during the pre-treatment period Of note results of DNA sequencing on the biopsy will be communicated to the treating oncologist to potentially inform post progression therapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None