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Copper Cu 64-DOTA-Trastuzumab PET in Predicting Response to Treatment With Ado-Trastuzumab Emtansine in Patients With Metastatic HER2 Positive Breast Cancer

Primary Purpose

Bone Metastases, HER2-positive Breast Cancer, Liver Metastases

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
fludeoxyglucose F 18
positron emission tomography
computed tomography
trastuzumab
copper Cu 64-DOTA-trastuzumab
positron emission tomography
ado-trastuzumab emtansine
laboratory biomarker analysis
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Bone Metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants must be women who have histological confirmation of metastatic invasive breast cancer that has metastasized outside the region of the primary tumor and axilla; biopsy must be obtained prior to initiation of chemotherapy; it should be performed within 28 days prior to enrollment (patients with a biopsy of recurrent disease that is HER2-positive and have not received HER2-directed therapy since the biopsy can exceed the 28-day window up to 6 months); patients must have metastatic disease in lung, liver, soft-tissue or bone to qualify for the study (more than one site is permissible)
  • At least 1 site of metastasis >= 20 mm in mean diameter must be identified
  • The cancer must over express HER2 as determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH)
  • Patients may not have received trastuzumab within 6 weeks of projected 64Cu-DOTA-trastuzumab/PET-CT
  • Participants must have normal cardiac ejection fraction
  • Ability to provide informed consent
  • Patients that may need dose reduction to commence cycle 1 treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Negative serum pregnancy test (female of childbearing potential only)
  • Patients must have adequate cardiac function; left ventricular ejection fraction (LVEF) >= 50% as determined by multi gated acquisition (MUGA) scan or echocardiogram

Exclusion Criteria:

  • Participants who have received trastuzumab within the prior 36 days
  • Participants who are not considered candidates for ado-trastuzumab-emtansine
  • No metastatic sites >= 20 mm
  • Concurrent malignancy other than skin cancer - Inability to provide informed consent

Sites / Locations

  • City of Hope Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic (copper Cu 64-DOTA-trastuzumab PET)

Arm Description

Patients undergo whole body fludeoxyglucose F 18 PET/CT. Patients then receive trastuzumab IV over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV and then undergo PET scans at 24 and 48 hours. Patients then receive ado-trastuzumab emtansine IV every 3 weeks until complete response or disease progression at the discretion of the treating oncologist. Patients undergo restaging by whole body fludeoxyglucose F 18 PET/CT every 6 weeks after initiation of treatment until disease progression.

Outcomes

Primary Outcome Measures

Relationship Between Average Tumor Uptake of Copper Cu 64-DOTA-trastuzumab as Measured by PET and Patient Best Response
Relationship between patient best response to T-DM1 and measured tumor uptake of 64Cu-DOTA-trastuzumab employed a t-test with a 0.05 two-sided significance level comparing average uptake in responsive vs non-responsive patients. Tumor uptake measured as SUV defined as SUV = AC(tsc) Wb /[Dinj exp(-λ(tsc - tinj)] , where AC(tsc) is the activity concentration in the volume of interest (VOI, e. g., a tumor), Wb is the patient's body weight, Dinj is the activity injected at time tinj, and λ is the decay constant for the injected radioisotope. AC(tsc) is determined from the spatial density of counts acquired from the VOI. Tumor uptake was measured in terms of maximum voxel standardized uptake value, SUVmax. Response assessment adhered to Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST 1.0).
Relationship Between Tumor Minimum Uptake of Copper Cu 64-DOTA-trastuzumab as Measured by PET and Patient Best Response
Relationship between patient best response to T-DM1 and measured tumor uptake of 64Cu-DOTA-trastuzumab employed a t-test with a 0.05 two-sided significance level comparing minimum uptake in responsive vs non-responsive patients. Tumor uptake measured as SUV defined as SUV = AC(tsc) Wb /[Dinj exp(-λ(tsc - tinj)] , where AC(tsc) is the activity concentration in the volume of interest (VOI, e. g., a tumor), Wb is the patient's body weight, Dinj is the activity injected at time tinj, and λ is the decay constant for the injected radioisotope. AC(tsc) is determined from the spatial density of counts acquired from the VOI. Tumor uptake was measured in terms of minimum voxel standardized uptake value, SUVmin. Response assessment adhered to Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST 1.0).

Secondary Outcome Measures

Full Information

First Posted
August 25, 2014
Last Updated
February 21, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02226276
Brief Title
Copper Cu 64-DOTA-Trastuzumab PET in Predicting Response to Treatment With Ado-Trastuzumab Emtansine in Patients With Metastatic HER2 Positive Breast Cancer
Official Title
A Pilot Study of 64Cu-DOTA-Trastuzumab Positron Emission Tomography in Treatment of Advanced HER2 Positive Breast Cancer With the Antibody Drug Conjugate Ado-trastuzumab Emtansine
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 7, 2015 (undefined)
Primary Completion Date
December 7, 2021 (Actual)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This pilot clinical trial studies how well copper Cu 64-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography (PET) works in predicting response to treatment with ado-trastuzumab emtansine in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer that has spread to other places in the body. Copper Cu 64-DOTA-trastuzumab is a chemotherapy drug (trastuzumab) attached to a radioactive substance. Diagnostic procedures using PET may allow scanners to take pictures of where the drug travels in the body and may help doctors identify which patients may benefit from treatment with ado-trastuzumab emtansine.
Detailed Description
PRIMARY OBJECTIVES: I. Correlate uptake of 64Cu-DOTA-trastuzumab (copper Cu 64-DOTA-trastuzumab) PET by individual tumors with subsequent tumor response to ado-trastuzumab emtansine as assessed by serial 18F-fludeoxyglucose (FDG) (fludeoxyglucose F 18)/PET-computed tomography (CT). II. Compare tumor uptake of 64Cu-DOTA-trastuzumab PET between patients who do and patients who do not respond to ado-trastuzumab emtansine. III. Obtain tumor tissue for subsequent assessment of the presence of putative molecular mechanisms of resistance (MMRs) to ado-trastuzumab emtansine. When funding becomes available, those samples will be used to explore the correlation between the presence of MMRs as assessed by histopathology and tumor response to ado-trastuzumab emtansine both in univariate analysis and in combination with tumor uptake of 64Cu-DOTA-trastuzumab as measured with PET/CT. OUTLINE: Patients undergo whole body fludeoxyglucose F 18 PET/CT. Patients then receive trastuzumab intravenously (IV) over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV and then undergo PET scans at 24 and 48 hours. Patients then receive ado-trastuzumab emtansine IV every 3 weeks until complete response or disease progression at the discretion of the treating oncologist. Patients undergo restaging by whole body fludeoxyglucose F 18 PET/CT every 6 weeks for 1 year after initiation of treatment until disease progression. After completion of study treatment, patients are followed up for 1 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bone Metastases, HER2-positive Breast Cancer, Liver Metastases, Lung Metastases, Recurrent Breast Cancer, Soft Tissue Metastases, Stage IV Breast Cancer

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Diagnostic (copper Cu 64-DOTA-trastuzumab PET)
Arm Type
Experimental
Arm Description
Patients undergo whole body fludeoxyglucose F 18 PET/CT. Patients then receive trastuzumab IV over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV and then undergo PET scans at 24 and 48 hours. Patients then receive ado-trastuzumab emtansine IV every 3 weeks until complete response or disease progression at the discretion of the treating oncologist. Patients undergo restaging by whole body fludeoxyglucose F 18 PET/CT every 6 weeks after initiation of treatment until disease progression.
Intervention Type
Radiation
Intervention Name(s)
fludeoxyglucose F 18
Other Intervention Name(s)
18FDG, FDG
Intervention Description
Undergo fludeoxyglucose F 18 PET/CT
Intervention Type
Procedure
Intervention Name(s)
positron emission tomography
Other Intervention Name(s)
FDG-PET, PET, PET scan, tomography, emission computed
Intervention Description
Undergo fludeoxyglucose F 18 PET/CT
Intervention Type
Procedure
Intervention Name(s)
computed tomography
Other Intervention Name(s)
tomography, computed
Intervention Description
Undergo fludeoxyglucose F 18 PET/CT
Intervention Type
Biological
Intervention Name(s)
trastuzumab
Other Intervention Name(s)
anti-c-erB-2, Herceptin, MOAB HER2
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
copper Cu 64-DOTA-trastuzumab
Other Intervention Name(s)
64Cu-DOTA-trastuzumab
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
positron emission tomography
Other Intervention Name(s)
FDG-PET, PET, PET scan, tomography, emission computed
Intervention Description
Undergo copper Cu-DOTA-trastuzumab PET
Intervention Type
Biological
Intervention Name(s)
ado-trastuzumab emtansine
Other Intervention Name(s)
Kadcyla, T-DM1, trastuzumab-DM1, trastuzumab-MCC-DM1, trastuzumab-MCC-DM1 antibody-drug conjugate
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Relationship Between Average Tumor Uptake of Copper Cu 64-DOTA-trastuzumab as Measured by PET and Patient Best Response
Description
Relationship between patient best response to T-DM1 and measured tumor uptake of 64Cu-DOTA-trastuzumab employed a t-test with a 0.05 two-sided significance level comparing average uptake in responsive vs non-responsive patients. Tumor uptake measured as SUV defined as SUV = AC(tsc) Wb /[Dinj exp(-λ(tsc - tinj)] , where AC(tsc) is the activity concentration in the volume of interest (VOI, e. g., a tumor), Wb is the patient's body weight, Dinj is the activity injected at time tinj, and λ is the decay constant for the injected radioisotope. AC(tsc) is determined from the spatial density of counts acquired from the VOI. Tumor uptake was measured in terms of maximum voxel standardized uptake value, SUVmax. Response assessment adhered to Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST 1.0).
Time Frame
Baseline
Title
Relationship Between Tumor Minimum Uptake of Copper Cu 64-DOTA-trastuzumab as Measured by PET and Patient Best Response
Description
Relationship between patient best response to T-DM1 and measured tumor uptake of 64Cu-DOTA-trastuzumab employed a t-test with a 0.05 two-sided significance level comparing minimum uptake in responsive vs non-responsive patients. Tumor uptake measured as SUV defined as SUV = AC(tsc) Wb /[Dinj exp(-λ(tsc - tinj)] , where AC(tsc) is the activity concentration in the volume of interest (VOI, e. g., a tumor), Wb is the patient's body weight, Dinj is the activity injected at time tinj, and λ is the decay constant for the injected radioisotope. AC(tsc) is determined from the spatial density of counts acquired from the VOI. Tumor uptake was measured in terms of minimum voxel standardized uptake value, SUVmin. Response assessment adhered to Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST 1.0).
Time Frame
Up to 1 year

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must be women who have histological confirmation of metastatic invasive breast cancer that has metastasized outside the region of the primary tumor and axilla; biopsy must be obtained prior to initiation of chemotherapy; it should be performed within 28 days prior to enrollment (patients with a biopsy of recurrent disease that is HER2-positive and have not received HER2-directed therapy since the biopsy can exceed the 28-day window up to 6 months); patients must have metastatic disease in lung, liver, soft-tissue or bone to qualify for the study (more than one site is permissible) At least 1 site of metastasis >= 20 mm in mean diameter must be identified The cancer must over express HER2 as determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) Patients may not have received trastuzumab within 6 weeks of projected 64Cu-DOTA-trastuzumab/PET-CT Participants must have normal cardiac ejection fraction Ability to provide informed consent Patients that may need dose reduction to commence cycle 1 treatment Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Negative serum pregnancy test (female of childbearing potential only) Patients must have adequate cardiac function; left ventricular ejection fraction (LVEF) >= 50% as determined by multi gated acquisition (MUGA) scan or echocardiogram Exclusion Criteria: Participants who have received trastuzumab within the prior 36 days Participants who are not considered candidates for ado-trastuzumab-emtansine No metastatic sites >= 20 mm Concurrent malignancy other than skin cancer - Inability to provide informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joanne Mortimer
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Copper Cu 64-DOTA-Trastuzumab PET in Predicting Response to Treatment With Ado-Trastuzumab Emtansine in Patients With Metastatic HER2 Positive Breast Cancer

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