Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Pertuzumab

Antineoplastic Agents, Immunological

Blood specimens tested for circulating tumor cells followed by systemic treatment based on assay results with either trastuzumab or pertuzumab

Patients with HER2-negative metastatic breast cancer will be identified, and blood specimens will be obtained from each participant. The PRO Onc Assay will be performed on CTCs isolated from these specimens. When clinically indicated, fine needle aspiration biopsy will also be obtained and submitted for the PRO Onc Assay.

PRO Onc Assay and Treatment

8 mg/kg IV loading dose, followed by 6 mg /kg IV every 3 weeks until progressive disease or unacceptable toxicity with evaluations performed every 8 weeks

840 mg IV loading dose, followed by 420 IV every 3 weeks until progressive disease or unacceptable toxicity with evaluations performed every 8 weeks

John D. Hainsworth, M.D.

This trial will evaluate the clinical significance of the PRO Onc assay and will assess the efficacy of HER2-targeted therapy in patients with HER2-negative breast cancer who have been identified as having HER2 overexpression/activation by the PRO Onc Assay.

This two-part trial is designed to evaluate the clinical significance of the PRO Onc assay when used in patients with metastatic HER2-negative breast cancer. The first part of this study will determine the incidence of HER overexpression/activation, as determined by the PRO Onc assay, in patients previously judged to have HER2-negative breast cancer by FISH analysis. Blood specimens will be obtained from patients with HER2-negative breast cancer; CTCs will then be isolated and tested for HER2 overexpression/activation using the PRO Onc Assay. When clinically indicated, fine needle aspiration biopsy will also be obtained and submitted for the PRO Onc Assay. If the incidence of HER2 overexpression/activation, as determined by the PRO Onc Assay, is \>10%, the study will proceed to Part 2. Part 2 of this study will assess the efficacy of HER2-targeted therapy in a group of patients with HER2-negative breast cancer who are identified as having HER2 overexpression/activation by the PRO Onc Assay. Patients will be treated with either trastuzumab or pertuzumab. Patients who progress during the first 8 weeks will have HER2-targeted treatment discontinued and will be removed from study. After 8 weeks, patients who have stable disease will be allowed to add chemotherapy to HER2-targeted therapy. Patients who have an objective response to single-agent, HER2-targeted therapy after 8 weeks will continue single-agent therapy.

Use of PRO Onc Assay to Assess HER2 in Patients With Metastatic Breast Cancer

Use of the PRO Onc Assay to Assess HER2 Overexpression and Activation in Patients With Metastatic Breast Cancer Whose Tumors Are HER2-Negative by Standard FISH Testing

The percentage of HER2-negative metastatic breast cancer (MBC) patients having an objective benefit from treatment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Includes patients with HER2 overexpression/activation as detected by PRO Onc Assay.

The percentage of patients having an objective benefit from treatment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Includes patients with HER2 overexpression as identified by the PRO Onc Assay.

The percentage of patients with HER2 activation (no overexpression) as identified by the PRO Onc Assay who experience an objective benefit from treatment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Includes patients with HER2-negative metastatic breast cancer (MBC) as determined by FISH testing.

Percentage of HER2-negative MBC patients (identified by FISH testing) having CTCs present in blood specimens.

Prometheus Laboratories

Genentech, Inc.

SCRI Development Innovations, LLC

Includes all patients with HER2 overexpression/activation (as identified by the PRO Onc Assay) who received study treatment

All Treated Patients

Patients Treated

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Excludes patients with no circulating tumor cells for the PRO Onc Assay

John D. Hainsworth, MD

HER2 overexpressed

HER2 activated

HER2 overexpressed and activated

No HER2 overexpression/activation detected

All Patients Evaluated by PRO Onc Assay

Part 1: The Incidence of HER2 Overexpression/Activation as Measured by the PRO Onc Assay

Part II: Objective Response Rate of HER2-negative Metastatic Breast Cancer (by FISH Testing)

All Patients

Includes all patients with blood drawn and analyzed for CTCs

Part I: The Incidence of Isolation of Circulating Tumor Cells (CTCs) From Blood Specimens

Includes patients with HER2 overexpression detected by the PRO Onc Assay

Part II: Objective Response Rate of Trastuzumab Therapy

Includes patients with only HER2 activation (no overexpression) as detected by the PRO Onc Assay

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