Clinical trial NCT02226276: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Bone Metastases
HER2-positive Breast Cancer
Liver Metastases
Lung Metastases
Recurrent Breast Cancer
Soft Tissue Metastases
Stage IV Breast Cancer
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-08-27
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Relationship Between Average Tumor Uptake of Copper Cu 64-DOTA-trastuzumab as Measured by PET and Patient Best Response
timeFrame: Baseline
measure: Relationship Between Tumor Minimum Uptake of Copper Cu 64-DOTA-trastuzumab as Measured by PET and Patient Best Response
timeFrame: Up to 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Joanne Mortimer
role: PRINCIPAL_INVESTIGATOR
References: