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

Stage IIIA Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02827877
• Other study ID #: 16079
• Secondary ID: FWA 00000692
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 15, 2016
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: December 30, 2024
• Est. primary completion date: July 2, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Radiation:
• Copper Cu 64-DOTA-Trastuzumab
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• Pertuzumab
Given IV

Procedure:
• Positron Emission Tomography
Undergo PET
• Therapeutic Conventional Surgery
Undergo surgery

Biological:
• Trastuzumab
Given IV

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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