Characterization of Circulating Tumor Cells Captured by c-MET (CTC-MET)

This pilot study will aim to determine whether circulating tumor cells (CTCs) can be captured using the novel cMET based ferrofluid. The primary objective of this pilot study will be to describe the numbers of c-MET expressing cells that can be detected by the c-MET CTC capture technique. These data will be separated by disease site. The investigator will also describe the detection rates of both the c-MET CTC capture and the EpCAM CTC capture techniques in each patient, also separated by disease site.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Prostate Cancer; Bladder Cancer; Non-small Cell Lung Cancer; Advanced MET Amplified Solid Tumor
• Intervention / Treatment: Device: Mesenchymal-marker based ferrofluid (c-MET); Device: Epithelial cell adhesion molecule (EpCAM) ferrofluid

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Prostate cancer patients will be eligible for inclusion in this study only if all of the following criteria apply:

1. Histologically confirmed diagnosis of adenocarcinoma of the prostate. Small cell or neuroendocrine tumors of the prostate are also permitted.
2. Clinical or radiographic evidence of metastatic disease.
3. Castrate levels of testosterone (<50 ng/dl)
4. Enrollment prior to the initiation of a new systemic therapy.

5. Evidence of disease progression on or following most recent therapy as evidenced by either of the following:

   • Two consecutive PSA levels greater than the PSA nadir achieved on ADT and most recent therapy, separated by greater than one week
   • Radiographic evidence of disease progression as defined by new bone scan lesions or growth of soft tissue/visceral metastases >1 cm in diameter (2 cm for lymph nodes).
   • Clinical progression of disease with cutaneous lesions or palpable lesions in absence of radiographic progression
6. Age > 18 years.
7. Ability to understand and the willingness to sign a written informed consent document.

Renal cell carcinoma patients will be eligible for inclusion in this study only if all of the following inclusion criteria apply:

1. Histologically confirmed diagnosis of invasive renal cell carcinoma (all histologies)
2. Clinical or radiographic evidence of metastatic disease.

3. Evidence of disease progression on the current or following the most recent therapy, as defined by one of the following:

   • A new soft tissue/visceral/lymph node/bone metastatic lesion
   • Growth of existing soft tissue/visceral/lymph node/bone metastases as determined by the investigator
   • Clinical progression of disease with cutaneous lesions or palpable lesions in absence of radiographic progression
4. For clear cell carcinoma, refractory to treatment with VEGF inhibitors as defined by progression on VEGF therapy within 1 year of starting VEGF therapy. For non-clear cell histologies, any line of systemic therapy.
5. Enrollment prior to the initiation of a new systemic therapy.
6. Age > 18 years.
7. Ability to understand and the willingness to sign a written informed consent document.

Bladder cancer patients will be eligible for inclusion in this study only if all of the following inclusion criteria apply:

1. Histologically confirmed diagnosis of invasive bladder transitional cell carcinoma, adenocarcinoma, squamous cell carcinoma, or small cell carcinoma.
2. Metastatic disease with either bone or visceral metastatic lesions, or clinically symptomatic with metastatic disease.

3. Progression of disease on or following the most recent treatment as evidenced by one of the following:

   • A new soft tissue/visceral/lymph node/bone metastatic lesion
   • Growth of existing soft tissue/visceral/lymph node/bone metastases as determined by the investigator.
   • Clinical progression of disease with cutaneous lesions, palpable lesions, pleural effusions, or ascites in absence of radiographic progression
4. Enrollment prior to the initiation of a new systemic therapy.
5. Age > 18 years.
6. Ability to understand and the willingness to sign a written informed consent document.

Gastric cancer (including gastroesophageal junction) patients will be eligible for inclusion in this study only if all of the following inclusion criteria apply:

1. Histologically confirmed diagnosis of invasive gastric or distal esophageal adenocarcinoma.
2. Clinical or radiographic evidence of metastatic disease.

3. Evidence of disease progression on or following the most recent therapy, as defined by one of the following:

   • New soft tissue/visceral/lymph node/bone metastatic lesion
   • Growth of existing soft tissue/visceral/lymph node/bone metastases as determined by the investigator
   • Clinical progression of disease with cutaneous lesions, palpable lesions, pleural effusions, or ascites in absence of radiographic progression
4. Enrollment prior to the initiation of a new systemic therapy.
5. Age > 18 years.
6. Ability to understand and the willingness to sign a written informed consent document.

Colorectal cancer patients will be eligible for inclusion in this study only if all of the following inclusion criteria apply:

1. Histologically confirmed diagnosis of invasive colorectal adenocarcinoma.
2. Clinical or radiographic evidence of metastatic disease.

3. Evidence of disease progression on the current or following the most recent therapy, as defined by one of the following:

   • New soft tissue/visceral/lymph node/bone metastatic lesion
   • Growth of existing soft tissue/visceral/lymph node/bone metastases as determined by the investigator
   • Clinical progression of disease with cutaneous lesions, palpable lesions, pleural effusions, or ascites in absence of radiographic progression
4. Enrollment prior to the initiation of a new systemic therapy.
5. Age > 18 years.
6. Ability to understand and the willingness to sign a written informed consent document.

Pancreatic cancer patients will be eligible for inclusion in this study only if all of the following inclusion criteria apply:

1. Histologically confirmed diagnosis of invasive pancreatic adenocarcinoma.
2. Clinical or radiographic evidence of metastatic disease.
3. Enrollment prior to the initiation of a new systemic therapy.
4. Age > 18 years.
5. Ability to understand and the willingness to sign a written informed consent document.

Advanced, MET amplified, solid tumor patients will be eligible for inclusion in this study only if all of the following inclusion criteria apply:

1. Histologically confirmed diagnosis of cancer (any kind)
2. MET gene amplification by FISH, CISH, rtPCR, or other assay as determined by the investigator.
3. Clinical or radiographic evidence of metastatic disease.
4. Age > 18 years.
5. Ability to understand and the willingness to sign a written informed consent document.

Non-Small Cell Lung Cancer (NSCLC) patients will be eligible for inclusion in this study only if all of the following inclusion criteria apply:

1. Histologically confirmed diagnosis of invasive non-small cell carcinoma of the lung (includes adenocarcinoma, squamous cell carcinoma, large cell carcinoma, adenosquamous, and carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements; does not include carcinoid tumor or neuroendocrine carcinoma).
2. Metastatic disease with either bone or visceral metastatic lesions, or clinically symptomatic with metastatic disease.

3. Progression of disease on or following the most recent treatment as evidenced by one of the following:

   • A new soft tissue/visceral/lymph node/bone metastatic lesion
   • Growth of existing soft tissue/visceral/lymph node/bone metastases as determined by the investigator.
   • Clinical progression of disease with cutaneous lesions or palpable lesions in absence of radiographic progression
4. Progression of disease either on or following treatment with an EGFR inhibitor (such as erlotinib, gefitinib, or other EGFR-targeted therapy)
5. Enrollment prior to the initiation of a new systemic therapy.
6. Age > 18 years.
7. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

A patient will not be eligible for inclusion in this study if any of the following criteria apply:

1. History of intercurrent or past medical or psychiatric illness that would make participation in a blood drawing protocol difficult or not feasible at the discretion of the principal investigator or co-investigator(s).
2. Treatment with an anthracycline (including mitoxantrone, doxorubicin, epirubicin, and daunorubicin) within 1 week of CTC collection (applicable in prostate and gastric cancer patients), as anthracyclines cause auto-fluorescence of cells.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Prostate cancer; Mesenchymal-marker based ferrofluid (c-MET)	Device: Mesenchymal-marker based ferrofluid (c-MET); Device: Epithelial cell adhesion molecule (EpCAM) ferrofluid
Other: Renal cell carcinoma; Mesenchymal-marker based ferrofluid (c-MET)	Device: Mesenchymal-marker based ferrofluid (c-MET); Device: Epithelial cell adhesion molecule (EpCAM) ferrofluid
Other: Bladder cancer; Mesenchymal-marker based ferrofluid (c-MET)	Device: Mesenchymal-marker based ferrofluid (c-MET); Device: Epithelial cell adhesion molecule (EpCAM) ferrofluid
Other: Gastric cancer; Mesenchymal-marker based ferrofluid (c-MET)	Device: Mesenchymal-marker based ferrofluid (c-MET); Device: Epithelial cell adhesion molecule (EpCAM) ferrofluid
Other: Colorectal cancer; Mesenchymal-marker based ferrofluid (c-MET)	Device: Mesenchymal-marker based ferrofluid (c-MET); Device: Epithelial cell adhesion molecule (EpCAM) ferrofluid
Other: Pancreatic cancer; Mesenchymal-marker based ferrofluid (c-MET)	Device: Mesenchymal-marker based ferrofluid (c-MET); Device: Epithelial cell adhesion molecule (EpCAM) ferrofluid
Other: Non-small cell lung cancer; Mesenchymal-marker based ferrofluid (c-MET)	Device: Mesenchymal-marker based ferrofluid (c-MET); Device: Epithelial cell adhesion molecule (EpCAM) ferrofluid
Other: Advanced MET amplified solid tumor; Mesenchymal-marker based ferrofluid (c-MET)	Device: Mesenchymal-marker based ferrofluid (c-MET); Device: Epithelial cell adhesion molecule (EpCAM) ferrofluid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility	Feasibility as measured by successfully detecting at least one CTC in at least 2 out of 10 subjects within each disease site.	day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in the median number of CTCs	The difference in the median number of CTCs detected by each of the capture methods (novel and standard) will be calculated.	day 1
Association of the number of detectable CTCs with baseline clinical and pathologic disease characteristics.	Within each method, the patient will be used as the unit of observation to describe the association of number of detectable CTC cells with the following baseline characteristics: TNM staging, site of metastases (e.g., bone, liver, lymph nodes), Gleason sum (for PC), PSA (for PC), the number of prior hormone therapies (in PC), CEA (for colorectal cancer), the use of previous EGFR inhibitors and KRAS mutation status (for colorectal cancer), HER2 status and prior HER2 treatments (for gastric cancer), CA 19-9 (for pancreatic cancer), and number of prior chemotherapies.	day 1
Kinetics of CTCs over time during treatment with c-MET targeted therapies	Change is CTCs in patients with MET amplified tumors undergoing treatment with c-MET targeted therapies will be calculated.	8 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Prostate Cancer Foundation; Janssen Diagnostics, LLC

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): May 19, 2016
• Study Completion (Actual): July 19, 2016

Study Registration Dates

• First Submitted: March 3, 2014
• First Submitted That Met QC Criteria: March 4, 2014
• First Posted (Estimate): March 6, 2014

Study Record Updates

• Last Update Posted (Actual): August 1, 2017
• Last Update Submitted That Met QC Criteria: July 31, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Carcinoma, Renal Cell; Neoplastic Cells, Circulating
• Other Study ID Numbers: Pro00052149