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

NCT ID: NCT02226276

Last Updated: 2025-02-18

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-07

Study Completion Date

2025-10-30

Brief Summary

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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

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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.

Conditions

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Bone Metastases HER2-positive Breast Cancer Liver Metastases Lung Metastases Recurrent Breast Cancer Soft Tissue Metastases Stage IV Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Diagnostic (copper Cu 64-DOTA-trastuzumab PET)

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.

Group Type EXPERIMENTAL

fludeoxyglucose F 18

Intervention Type RADIATION

Undergo fludeoxyglucose F 18 PET/CT

positron emission tomography

Intervention Type PROCEDURE

Undergo fludeoxyglucose F 18 PET/CT

computed tomography

Intervention Type PROCEDURE

Undergo fludeoxyglucose F 18 PET/CT

trastuzumab

Intervention Type BIOLOGICAL

Given IV

copper Cu 64-DOTA-trastuzumab

Intervention Type RADIATION

Given IV

positron emission tomography

Intervention Type PROCEDURE

Undergo copper Cu-DOTA-trastuzumab PET

ado-trastuzumab emtansine

Intervention Type BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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fludeoxyglucose F 18

Undergo fludeoxyglucose F 18 PET/CT

Intervention Type RADIATION

positron emission tomography

Undergo fludeoxyglucose F 18 PET/CT

Intervention Type PROCEDURE

computed tomography

Undergo fludeoxyglucose F 18 PET/CT

Intervention Type PROCEDURE

trastuzumab

Given IV

Intervention Type BIOLOGICAL

copper Cu 64-DOTA-trastuzumab

Given IV

Intervention Type RADIATION

positron emission tomography

Undergo copper Cu-DOTA-trastuzumab PET

Intervention Type PROCEDURE

ado-trastuzumab emtansine

Given IV

Intervention Type BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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18FDG FDG FDG-PET PET PET scan tomography, emission computed tomography, computed anti-c-erB-2 Herceptin MOAB HER2 64Cu-DOTA-trastuzumab FDG-PET PET PET scan tomography, emission computed Kadcyla T-DM1 trastuzumab-DM1 trastuzumab-MCC-DM1 trastuzumab-MCC-DM1 antibody-drug conjugate

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

City of Hope Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joanne Mortimer

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2014-01812

Identifier Type: REGISTRY

Identifier Source: secondary_id

14099

Identifier Type: OTHER

Identifier Source: secondary_id

14099

Identifier Type: -

Identifier Source: org_study_id

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