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

Use of 64Cu-DOTA-Trastuzumab PET Imaging and Molecular Markers for Prediction of Response to Trastuzumab and Pertuzum-Based Neoadjuvant Therapy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; HER2 Positive Breast Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Trastuzumab; Procedure: Therapeutic Conventional Surgery; Procedure: Positron Emission Tomography; Biological: Pertuzumab; Radiation: Copper Cu 64-DOTA-Trastuzumab

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Trastuzumab; Given IV; Other Names: Herceptin; 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 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; Procedure: Therapeutic Conventional Surgery; Undergo surgery; Procedure: Positron Emission Tomography; Undergo PET; Other Names: PET Scan; Biological: Pertuzumab; Given IV; Other Names: Perjeta; 2C4; 2C4 Antibody; MoAb 2C4; Monoclonal Antibody 2C4; rhuMAb2C4; RO4368451; Radiation: Copper Cu 64-DOTA-Trastuzumab; Given IV; Other Names: 64Cu-DOTA-Trastuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to Neoadjuvant Chemotherapy Determined at Surgery (Lumpectomy or Mastectomy).	The response assessment is performed at the time of definitive surgery. Patients' disease will be staged in the conventional manner according to the AJCC. The primary endpoint is complete pathologic response defined as no evidence of residual invasive cancer in either the breast or regional lymph nodes.	Up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
SUV Measurement by 64Cu-DOTA Trastuzumab PET	First Scan SUV Maximum, measurement by 64Cu-DOTA trastuzumab PET SUV is "Standard Uptake Value". SUV = tumor activity concentration x patient body weight/injected activity decay-corrected to time of scan.	Baseline

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Joanne Mortimer, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2016
• Primary Completion (Actual): July 2, 2020
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: April 26, 2016
• First Submitted That Met QC Criteria: July 6, 2016
• First Posted (Estimated): July 11, 2016

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Trace Elements; Micronutrients; Trastuzumab; Copper; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Pertuzumab
• Other Study ID Numbers: 16079 (City of Hope Medical Center); FWA 00000692 (Registry Identifier: Federal-wide Assurance Number)