Harvest of CTCs From MBC Patients Using the Parsortix™ PC1 System (HOMING)

• ClinicalTrials.gov Identifier: NCT03427450
• Recruitment Status: Completed
• First Posted: February 9, 2018
• Last Update Posted: October 5, 2020
• Sponsor: Angle plc
• Information provided by (Responsible Party): Angle plc

Study Description

Brief Summary:

The purpose of this clinical study is to demonstrate that the Parsortix™ PC1 system enables the capture and harvest of circulating tumor cells (CTCs) from the peripheral blood of patients with metastatic breast cancer (MBC) and not from healthy volunteers (HVs). The study is also designed to demonstrate that the CTCs harvested by the Parsortix PC1 system from MBC patients can be used effectively for different types of evaluations (e.g. cytopathology, FISH, qPCR, RNAseq, etc.).

This is an investigational study. The Parsortix PC1 system is not FDA approved and is currently being used for research purposes only.

Condition or disease	Intervention/treatment
Healthy Volunteers; Breast Cancer, Metastatic	Diagnostic Test: Blood draw

Detailed Description:

Approximately 200 evaluable MBC patients (either newly diagnosed or patients with progressive/recurrent disease who are about to start a new line of therapy for the treatment of their disease) and 200 evaluable healthy volunteer (HV) subjects (healthy women with no history of cancer) will be enrolled at a minimum of three (3) US based clinical sites. Each subject will have information about their age race/ethnicity, height and weight, menopausal status, smoking status, pregnancy and/or nursing status, and a brief medical history captured at the time of enrollment. Blood will be drawn from each subject into three different EDTA tubes (minimum of ~7mL up to a maximum of ~23mL of whole blood) specifically for the purposes of this study. One of the blood tubes collected will be used for a complete blood count (CBC) with differential testing, while the other two tubes of blood will be processed on the Parsortix PC1 system for the capture and harvest of CTCs. The cells harvested from one of the blood tubes will be deposited onto a glass slide and automated Wright-Giemsa staining will be done to allow for identification of CTCs based on their cytologic features (e.g. size, shape, nuclear to cytoplasmic ratio, chromatin structure, etc.) by an expert cytopathologist. The cells harvested from the remaining blood tube will be used for one of three different evaluations: Fluorescence in-situ hybridization (FISH) for evaluation of Her-2/neu gene amplification, quantitative reverse-transcriptase real-time PCR (qRT-PCR) for evaluation of cancer related gene expression, or whole transcriptome sequencing (RNAseq) for determination of the expression patterns of breast cancer related genes.

Study Design

• Study Type: Observational
• Actual Enrollment: 421 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Harvest of Circulating Tumor Cells (CTCs) From Patients With Metastatic Breast Cancer (MBC) Using the Parsortix™ PC1 System
• Actual Study Start Date: March 29, 2018
• Actual Primary Completion Date: May 16, 2019
• Actual Study Completion Date: December 31, 2019

Groups and Cohorts

Group/Cohort	Intervention/treatment
Healthy Volunteers (Controls); A control population of healthy volunteers (HVs) consisting of women with no prior/current history of cancer and no known history of breast disease (the information obtained from the HVs may be 'self-reports', as complete medical records may not be available at the enrolling site for these control subjects), and with a broadly similar age range to the cancer patient study population. All eligible and consenting subjects will have blood draw.	Diagnostic Test: Blood draw; Blood collected will be processed on Parsortix PC1 system for capture and harvest of circulating tumor cells to be used in subsequent evaluations.
MBC Patients (Cancers); Women with either newly diagnosed metastatic breast cancer who are about to start a new line of therapy of any type for the treatment and/or management of their disease or those with currently progressive or recurrent disease (as determined by any means) will be eligible for enrollment into the cancer population. All eligible and consenting subjects will have blood draw.	Diagnostic Test: Blood draw; Blood collected will be processed on Parsortix PC1 system for capture and harvest of circulating tumor cells to be used in subsequent evaluations.

Outcome Measures

Primary Outcome Measures :

1. Incidence of CTC [ Time Frame: 1 day (At time of blood draw) ]
   Determine the proportion of MBC patients and healthy volunteers (HVs or controls) that have one or more observable CTCs (as determined by a qualified pathologist using cytological evaluation of Wright-Giemsa stained slides) harvested from their peripheral blood using the Parsortix PC1 system.

Secondary Outcome Measures :

1. CTC Enumeration [ Time Frame: 1 day (At time of blood draw) ]
   Quantify the number of observable CTCs (as determined by a qualified pathologist using cytological evaluation of Wright-Giemsa stained slides) harvested from the peripheral blood of each MBC patient and healthy volunteer (HV or control) and summarize separately for each group.

Other Outcome Measures:

1. Her2 FISH Evaluation [ Time Frame: 1 day (At time of blood draw) ]
   Demonstrate that CTCs harvested from peripheral blood of MBC patients by the Parsortix PC1 system and deposited onto slides can be evaluated by fluorescence in-situ hybridization (FISH) for Her-2/neu gene amplification.
2. qPCR Evaluation [ Time Frame: 1 day (At time of blood draw) ]
   Demonstrate that CTCs harvested from peripheral blood of MBC patients by the Parsortix PC1 system and deposited into an RNA preservation/lysis buffer can be evaluated using qPCR for analysis of cancer related gene expression.
3. RNAseq Evaluation [ Time Frame: 1 day (At time of blood draw) ]
   Demonstrate that CTCs harvested from peripheral blood of MBC patients by the Parsortix PC1 system and deposited into an RNA preservation/lysis buffer can be evaluated using whole genome sequencing (RNAseq) for determination of the expression patterns of breast cancer related genes.

Biospecimen Retention:   Samples With DNA

Cytology slides Her2 FISH slides mRNA cDNA

Eligibility Criteria

• Ages Eligible for Study: 22 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Healthy Volunteers: Female subjects at outpatient clinics whom a delegated physician and/or study coordinator believe may be eligible for the study will be approached by the delegated physician and/or study coordinator during their scheduled gynecology appointment or, if they are accompanying a breast cancer patient, during the scheduled appointment of the individual they are accompanying.

Metastatic Breast Cancer Patients: Eligible female subjects at outpatient clinics and/or under the care of investigators at the participating medical centers will be prospectively identified by the site principal investigator, sub-investigators, nurses and/or study coordinator.

Criteria

MBC Patient Inclusion Criteria

• Female >=22 years of age;

• Documented evidence of metastatic breast cancer (i.e. primary tumor histopathology of breast cancer and documented evidence of distant sites of metastasis by imaging, biopsy, or other means) that is either newly diagnosed or currently progressing / recurrent (disease progression / recurrence may be determined by any means, including RECIST v1.1 criteria, physical signs and symptoms, rising tumor markers, physician determination, etc.);

  • If newly diagnosed, have not yet started a new line of therapy of any type (e.g. hormonal, cytotoxic, targeted, etc.) for the treatment and/or management of their metastatic breast cancer;
  • If progressing or recurrent, any number of prior hormonal therapies, chemotherapies and/or biological/targeted therapies are allowed;
• Willing and able to provide informed consent and agree to complete all aspects of the study.

MBC Patient Exclusion Criteria

• Female subjects <=21 years old or male subjects;
• Concurrent other malignancies (except for a second primary breast cancer);
• Less than seven days since last administration of a cytotoxic agent;
• Unwilling or unable to provide informed consent or high risk that subject may not comply with protocol requirements.

HV Inclusion Criteria

• Females >=22 years of age;
• No known fever or active infections at the time of the blood collection;
• No known current diagnosis of acute inflammatory disease or chronic inflammation;
• No known current and/or prior history of malignancy, excluding skin cancers (squamous cell or basal cell);
• Willing and able to provide informed consent and agree to complete all aspects of the study.

HV Exclusion Criteria

• Female subjects <=21 years old or male subjects;
• Known illness at the time of the blood collection;
• Known current and/or prior history of malignancy, excluding skin cancers (squamous cell or basal cell);
• Unwilling or unable to provide informed consent or high risk that subject may not comply with protocol requirements (e.g. due to health and/or participation in other research studies).

Contacts and Locations

Locations

United States, California

University of Southern California

Los Angeles, California, United States, 90033

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, New York

University of Rochester Medical Center Wilmot Cancer Institute

Rochester, New York, United States, 14642

United States, Texas

UT MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Angle plc

Investigators

• Principal Investigator: Naoto Ueno, MD, PhD; UT MD Anderson Cancer Center

More Information

Publications:

Xu L, Mao X, Imrali A, Syed F, Mutsvangwa K, Berney D, Cathcart P, Hines J, Shamash J, Lu YJ. Optimization and Evaluation of a Novel Size Based Circulating Tumor Cell Isolation System. PLoS One. 2015 Sep 23;10(9):e0138032. doi: 10.1371/journal.pone.0138032. eCollection 2015.

Hvichia GE, Parveen Z, Wagner C, Janning M, Quidde J, Stein A, Muller V, Loges S, Neves RP, Stoecklein NH, Wikman H, Riethdorf S, Pantel K, Gorges TM. A novel microfluidic platform for size and deformability based separation and the subsequent molecular characterization of viable circulating tumor cells. Int J Cancer. 2016 Jun 15;138(12):2894-904. doi: 10.1002/ijc.30007. Epub 2016 Feb 26.

• Responsible Party: Angle plc
• ClinicalTrials.gov Identifier: NCT03427450
• Other Study ID Numbers: ANG-002
• First Posted: February 9, 2018
• Last Update Posted: October 5, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Angle plc:

circulating tumor cells; liquid biopsy; microfluidics

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases