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

HER2-positive Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02226276
• Other study ID #: 14099
• Secondary ID: NCI-2014-0181214
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 7, 2015
• Est. completion date: December 7, 2024

Study information

• Verified date: February 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: December 7, 2024
• Est. primary completion date: December 7, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bone Metastases
• Breast Neoplasms
• HER2-positive Breast Cancer
• Liver Metastases
• Lung Metastases
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Recurrent Breast Cancer
• Soft Tissue Metastases
• Stage IV Breast Cancer

Intervention

Radiation:
• fludeoxyglucose F 18
Undergo fludeoxyglucose F 18 PET/CT

Procedure:
• positron emission tomography
Undergo fludeoxyglucose F 18 PET/CT
• computed tomography
Undergo fludeoxyglucose F 18 PET/CT

Biological:
• trastuzumab
Given IV

Radiation:
• copper Cu 64-DOTA-trastuzumab
Given IV

Procedure:
• positron emission tomography
Undergo copper Cu-DOTA-trastuzumab PET

Biological:
• ado-trastuzumab emtansine
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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(-?(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 ? 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).	Baseline
Primary	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(-?(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 ? 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).	Up to 1 year