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

NCT ID: NCT02827877

Last Updated: 2025-11-14

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-15

Study Completion Date

2026-09-25

Brief Summary

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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

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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.

Conditions

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HER2 Positive Breast Carcinoma Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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.

Group Type EXPERIMENTAL

Copper Cu 64-DOTA-Trastuzumab

Intervention Type RADIATION

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pertuzumab

Intervention Type BIOLOGICAL

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Trastuzumab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Copper Cu 64-DOTA-Trastuzumab

Given IV

Intervention Type RADIATION

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pertuzumab

Given IV

Intervention Type BIOLOGICAL

Positron Emission Tomography

Undergo PET

Intervention Type PROCEDURE

Therapeutic Conventional Surgery

Undergo surgery

Intervention Type PROCEDURE

Trastuzumab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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64Cu-DOTA-Trastuzumab 2C4 2C4 Antibody MoAb 2C4 Monoclonal Antibody 2C4 Perjeta rhuMAb2C4 RO4368451 PET Scan ABP 980 Anti-c-ERB-2 Anti-c-erbB2 Monoclonal Antibody Anti-ERB-2 Anti-erbB-2 Anti-erbB2 Monoclonal Antibody Anti-HER2/c-erbB2 Monoclonal Antibody Anti-p185-HER2 c-erb-2 Monoclonal Antibody HER2 Monoclonal Antibody Herceptin Herceptin Biosimilar PF-05280014 Herceptin Trastuzumab Biosimilar PF-05280014 MoAb HER2 Monoclonal Antibody c-erb-2 Monoclonal Antibody HER2 PF-05280014 rhuMAb HER2 RO0452317 Trastuzumab Biosimilar ABP 980 Trastuzumab Biosimilar PF-05280014

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

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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FWA 00000692

Identifier Type: REGISTRY

Identifier Source: secondary_id

16079

Identifier Type: -

Identifier Source: org_study_id