Clinical trial NCT02827877: Cu64-DOTA-trastuzumab PET and Markers Predicting Response to Neoadjuvant Trastuzumab + Pertuzum in HER2+ Breast Cancer
Official title: Use of 64Cu-DOTA-Trastuzumab PET Imaging and Molecular Markers for Prediction of Response to Trastuzumab and Pertuzum-Based Neoadjuvant Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: HER2 Positive Breast Carcinoma
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-07-11
Enrollment: 18
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Response to Neoadjuvant Chemotherapy Determined at Surgery (Lumpectomy or Mastectomy).
timeFrame: Up to 1 year
Secondary outcomes:
Other outcomes:
measure: SUV Measurement by 64Cu-DOTA Trastuzumab PET
timeFrame: Baseline
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: