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

NCT01048099 | Completed Results

• 1 other identifier: SCRI BRE 166
• Study Type: interventional
• Target: 283
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Breast Cancer; Metastatic; PRO Onc Assay; FISH Testing; HER Negative; HER Overexpression; HER Activation

Outcome Measures

Primary Outcomes (3)

• Part II: Objective Response Rate of HER2-negative Metastatic Breast Cancer (by 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.

  18 months

• Part II: Objective Response Rate of Trastuzumab Therapy

  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.

  18 months

• Part II: Objective Response Rate of Pertuzumab Therapy

  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.

  18 months

Secondary Outcomes (2)

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

  12 months

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

  12 months

Study Arms (1)

PRO Onc Assay and Treatment

EXPERIMENTAL

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

Procedure: PRO Onc Assay and Treatment; Drug: Trastuzumab; Drug: Pertuzumab

Interventions

PRO Onc Assay and Treatment PROCEDURE

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.

Also known as: blood draw, fine needle aspiration, circulating tumor cells

PRO Onc Assay and Treatment

Trastuzumab DRUG

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

Also known as: Herceptin

PRO Onc Assay and Treatment

Pertuzumab DRUG

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

Also known as: Perjeta

PRO Onc Assay and Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part I
• Women with HER2-negative breast cancer, as defined by FISH testing. (FISH testing may have been performed on the primary tumor, or subsequently on a biopsy of a metastatic lesion.)
• Patients should be currently receiving chemotherapy, or scheduled to start chemotherapy (second-line or subsequent), for HER2-negative metastatic breast cancer.
• To begin protocol treatment, patients must have progressed after at least 1 previous chemotherapy regimen for metastatic breast cancer.
• Patients who are ER/PR positive or negative are eligible. ER/PR positive patients should be refractory to hormonal therapy, or not good candidates for hormonal therapy due to clinical features.
• ECOG performance status of 0, 1 or 2.
• Adequate recovery from recent surgery; ≥ 1 week must have elapsed from the time of a minor surgery; ≥ 4 weeks must have elapsed from the time of a major surgery.
• Patients must have measurable disease per RECIST criteria.
• Laboratory values as follows: Absolute neutrophil count (ANC) ≥1500/μL Hemoglobin (Hgb) ≥10 g/dL Platelets ≥100,000/L AST or ALT and alkaline phosphatase (ALP) must be \<2.5 x ULN, or \<5 x ULN in patients with liver metastases. Total bilirubin \<1.5 x the institutional ULN Serum creatinine \<1.5 x institutional ULN or calculated creatinine clearance ≥45 mL/min
• Patients from Part 1 who have HER2 overexpression/activation identified by the PRO Onc Assay may enter the treatment portion of Part 2, if they meet all Part 2 eligibility criteria.
• Life expectancy of ≥ 12 weeks.
• Patient must be accessible for treatment and follow-up.
• Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.
• Part II
• Women with HER2-negative breast cancer, as defined by FISH testing. (FISH testing may have been performed on the primary tumor, or subsequently on a biopsy of a metastatic lesion.)

You may not qualify if:

• Ejection fraction ≥ 50%, as measured by echocardiogram (ECHO) or MUGA.
• Part I:
• Patients currently responding to hormonal therapy.
• Previous treatment with any HER2-targeted agent.
• Patients with meningeal metastases.
• Patients who are not considered likely candidates for subsequent therapy after next progression of metastatic breast cancer.
• Women who are pregnant or lactating.
• Patients with New York Heart Association class II or greater congestive heart failure.
• Any of the following ≤6 months prior to starting study treatment:
• myocardial infarction;
• severe unstable angina;
• ongoing cardiac dysrhythmia
• Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements.
• Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
• Use of any non-approved or investigational agent ≤ 30 days of administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Prometheus Laboratories: collaborator
• Genentech, Inc.: collaborator

Study Sites (7)

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists

St. Petersburg, Florida, 33705, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23230, United States

Location

Related Publications (1)

• Hainsworth JD, Murphy PB, Alemar JR, Daniel BR, Young RR, Yardley DA. Use of a multiplexed immunoassay (PRO Onc assay) to detect HER2 abnormalities in circulating tumor cells of women with HER2-negative metastatic breast cancer: lack of response to HER2-targeted therapy. Breast Cancer Res Treat. 2016 Nov;160(1):41-49. doi: 10.1007/s10549-016-3969-7. Epub 2016 Sep 8.

  PMID: 27632289 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Therapeutics; Blood Specimen Collection; Biopsy, Fine-Needle; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Biopsy, Needle; Biopsy; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: John D. Hainsworth, MD
• Organization: Sarah Cannon Research Institute

asksarah@scresearch.net

1-877-691-7274

Study Officials

• John D. Hainsworth, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 13, 2010
• Study Start: January 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: January 29, 2016
• Results First Posted: January 29, 2016

Record last verified: 2015-12

Locations

US (7)