Cu64-DOTA-trastuzumab PET and Markers Predicting Response to Neoadjuvant Trastuzumab + Pertuzum in HER2+ Breast Cancer

City of Hope

Status and phase

Active, not recruiting

Phase 2

Conditions

Stage IIIA Breast Cancer

Stage IIIB Breast Cancer

HER2 Positive Breast Carcinoma

Stage IIIC Breast Cancer

Treatments

Procedure: Therapeutic Conventional Surgery

Procedure: Positron Emission Tomography

Other: Laboratory Biomarker Analysis

Biological: Pertuzumab

Biological: Trastuzumab

Radiation: Copper Cu 64-DOTA-Trastuzumab

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT02827877

16079 (Other Identifier)

FWA 00000692 (Registry Identifier)

Details and patient eligibility

About

This phase II trial studies how well copper Cu64-DOTA-trastuzumab positron emission tomography (PET) works in predicting response to treatment with trastuzumab and pertuzumab before surgery in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer that has spread from where it started to nearby tissue or lymph nodes. Diagnostic procedures, such as copper Cu 64 DOTA-trastuzumab PET, may help predict a patient's response to trastuzumab and pertuzumab before surgery in patients with locally advanced HER2 positive breast cancer.

Full description

PRIMARY OBJECTIVES:

I. To evaluate the standardized uptake value maximum (SUVmax) in patients with previously untreated HER2+ breast cancer.

SECONDARY OBJECTIVES:

I. To evaluate if the uptake of copper 64 Cu-64-DOTA-trastuzumab, a proposed indicator of responsiveness to HER2-directed therapy, correlates with serpin peptidase inhibitor alpha-1 antiproteinase, antitrypsin, member 1 gene (SERPINA1) expression, which has been shown to be associated with estrogen receptor positive (ER+)/ HER2+ patient survival, both in the HER2+/ER+ patients and in all patients.

II. To compare uptake of copper Cu 64-DOTA-trastuzumab in the patients with complete pathologic response (pCR) versus (vs) non-pCR patients.

OUTLINE:

Patients receive trastuzumab intravenously (IV) over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV on day 0. Patients undergo PET scans at 18-24 and 42-48 hours, on day 1 and 2. Within 4 days after completion of PET scans, patients then receive trastuzumab IV over 30-90 minutes weekly or every 3 weeks and pertuzumab IV over 30-60 minutes. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after 6 cycles of trastuzumab and pertuzumab.

After completion of study treatment, patients are followed up for 1 year.

Enrollment

18 patients

Sex

Female

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Participants must be women who have histological confirmation of HER2 positive breast cancer
The primary tumor must be >= 2.0cm in size and/or have biopsy proven axillary nodes that are >= 2.0cm in size by mammography, ultrasound, or magnetic resonance imaging (MRI)
The current cancer must over express HER2 as determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH)
Patients may not have received prior HER2 directed therapies
Participants must have normal cardiac ejection fraction (per label, as defined as institutional normal)
Planned neoadjuvant therapy with six cycles of combined pertuzumab, trastuzumab and chemotherapy
Ability to provide informed consent
Negative Serum Pregnancy test

Exclusion criteria

Participants who are not considered candidates for pertuzumab + trastuzumab + chemotherapy
Concurrent malignancy other than non-melanoma skin cancer
Patients must not have known metastatic disease
Patients must not have received prior treatment for the current breast cancer

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

18 participants in 1 patient group

Treatment (trastuzumab, copper Cu 64-DOTA-trastuzumab PET)

Experimental group

Description:

Patients receive trastuzumab IV over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV on day 0. Patients undergo PET scans at 18-24 and 42-48 hours, on day 1 and day 2. Within 4 days after completion of PET scans, patients receive trastuzumab IV over 30-90 minutes weekly or every 3 weeks and pertuzumab IV over 30-60 minutes. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after 6 cycles of trastuzumab and pertuzumab.