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A Microdose Evaluation Study of ABY-029 in Primary Sarcoma

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ClinicalTrials.gov Identifier: NCT03154411
Recruitment Status : Recruiting
First Posted : May 16, 2017
Last Update Posted : March 30, 2018
Sponsor:
Collaborator:
Dartmouth College
Information provided by (Responsible Party):
Eric R. Henderson, Dartmouth-Hitchcock Medical Center

Brief Summary:

The primary study objective is to determine if microdoses of ABY-029 (up to 6X) lead to detectable signals (defined as signal-to-noise ratio, SNR ≥10, with the Odyssey NIR scanner in sampled tissues with an EGFR pathology score ≥ 1 based on histological staining and compare SNR to tissues with an EGFR pathology score < 1).

The secondary study objective is to assess if the spatial patterns of EGFR expression correlate with the tumor targeting of ABY-029 detection by NIR scanner relative to histopathology diagnosis, and other indicators (e.g. proliferation, infiltration, etc.) as the gold standard, and to measure the molecular uptake and concentration of ABY-029 in resected specimens.


Condition or disease Intervention/treatment Phase
Primary Soft-tissue Sarcoma Drug: ABY-029 Early Phase 1

Detailed Description:

The investigators plan to enroll a minimum of 12 and a maximum of 18 adult patients with a diagnosis of primary soft-tissue sarcoma in this open label, single center, clinical trial of ABY-029. Two cohorts will be enrolled with a minimum of 6 and a maximum of 12 subjects in Cohort 1 and 6 patients in Cohort 2. Cohort 1 will include patients with an EGFR pathology score ≥ 1; Cohort 2 will include patients with an EGFR pathology score of < 1 (control).

Initial diagnostic biopsy specimens will be analyzed for EGFR positivity by immunohistochemistry following routine diagnostic processing by Pathologist. Patients will be administered a single intravenous dose of ABY-029 1-3 hours before surgery. Following tumor excision, the tumor will be transported to the Pathologist and will be inked and sectioned. Following sectioning the tumor will be imaged using a near-infrared scanner and fiber-probe based system. Quantitative measurements of fluorophore concentration will be measured for tumors with EGFR pathology score ≥ 1 and compared to those with EGFR pathology score < 1. Quantitative mapping of fluorophore concentration will be correlated with local EGFR concentration and blood vessel density. Upon specimen analysis, fluorophore measurements will be taken from normal, marginal tissues (e.g. skeletal muscle, adipose) in addition to the tumor. Average EGFR concentration and blood vessel density will be determined for each tumor through histological analysis of sections by routine sarcoma protocol and analysis guided by regional variations in ABY-029 concentration based upon near-infrared scan results.

The protocol is not a safety study since no physiological effects are expected at microdose levels of ABY-029. No diagnostic or therapeutic intent is proposed, and administration of the study drug is not intended to alter the extent of planned tumor resection during the surgical procedure.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: open label
Primary Purpose: Basic Science
Official Title: A Phase 0 Open Label, Single-center Clinical Trial of ABY-029, an Anti-EGFR Fluorescence Imaging Agent Via Single Intravenous Injection to Subjects With Primary Sarcoma.
Actual Study Start Date : August 30, 2017
Estimated Primary Completion Date : December 1, 2018
Estimated Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ABY-029
ABY-029 will be administered prior to surgery and tissue will be examined ex vivo to determine binding with EGFR positive tumor tissue.
Drug: ABY-029
A minimum of 12 and a maximum of 18 adult patients with a diagnosis of primary soft-tissue sarcoma will be enrolled. Initial diagnostic biopsy specimens will be analyzed for EGFR positivity by immunohistochemistry following routine diagnostic processing by Pathologist. Patients will be administered a single intravenous dose of ABY-029 1-3 hours before surgery. Two cohorts will be enrolled with a minimum of 6 and a maximum of 12 subjects in Cohort 1 and 6 patients in Cohort 2. Cohort 1 will include patients with an EGFR pathology score ≥ 1; Cohort 2 will include patients with an EGFR pathology score of < 1 (control).
Other Names:
  • ABY-029 trifluoroacetate salt
  • IRDye® 800CW Maleimide labeled Affibody peptide




Primary Outcome Measures :
  1. Signal detection [ Time Frame: Day of surgery, up to 1 week after surgery ]
    Following tumor excision, the tumor will be inked and sectioned and imaged using a near-infrared scanner and fiber-probe based system. Quantitative measurements of fluorophore concentration will be measured for tumors with EGFR pathology score ≥ 1 and compared to those with EGFR pathology score < 1.


Secondary Outcome Measures :
  1. Correlation of spatial patterns of EGFR expression [ Time Frame: within 1 week of surgery ]
    Quantitative mapping of fluorophore concentration will be correlated with local EGFR concentration and blood vessel density.

  2. molecular uptake and ABY-029 concentration [ Time Frame: within 1 week of surgery ]
    Fluorophore measurements will be taken from normal, marginal tissues (e.g. skeletal muscle, adipose) in addition to the tumor. Average EGFR concentration and blood vessel density will be determined for each tumor through histological analysis of sections by routine sarcoma protocol and analysis guided by regional variations in ABY-029 concentration based upon near-infrared scan results.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Preoperative histological diagnosis of primary sarcoma.
  2. Tumor judged to be suitable for open surgical resection based on preoperative imaging studies.
  3. Valid informed consent by subject.
  4. Age ≥ 18 years old.

Exclusion Criteria:

  1. Pregnant women or women who are breast feeding.
  2. Patients on any experimental anti-EGFR targeted therapies, either investigational or FDA approved.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03154411


Contacts
Contact: Keith D Paulsen, PhD 603-646-2695 Keith.D.Paulsen@Dartmouth.edu

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Dartmouth College
Investigators
Principal Investigator: Eric R Henderson, MD Dartmouth-Hitchcock Medical Center

Responsible Party: Eric R. Henderson, Principal Investigator, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT03154411     History of Changes
Other Study ID Numbers: D16143
First Posted: May 16, 2017    Key Record Dates
Last Update Posted: March 30, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eric R. Henderson, Dartmouth-Hitchcock Medical Center:
ABY-029
Affibody
molecular fluorescence-guided surgery
Epidermal Growth Factor Receptor (EGFR)

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms