Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of HS-196, an HSP90 Inhibitor-linked NIR Probe for Solid Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03333031
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : September 23, 2019
Sponsor:
Information provided by (Responsible Party):
Herbert Lyerly, Duke University

Brief Summary:
HS-196 is near infrared red (NIR)-tethered HSP90 inhibitor for clinical imaging of selective tumor binding. HS-196 consists of a HSP90 inhibitor that binds competitively to the Hsp90 ATP binding domain connected by a linker to a contrast agent (near infrared (NIR) dye) that can be used for imaging. HS-196 can freely enter tumor cells to selectively bind Hsp90. Due to the the NIR dye, HS-196 accumulation in the malignant cells allows for specific visualization of tumors within the body.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: HS-196 Phase 1

Detailed Description:

The product to be tested under this IND, HS-196, is a tumor imaging agent.

Hsp90 (heat shock protein 90) is a chaperone protein that aids in the folding, stabilization, and degradation of cellular proteins and is found in virtually all living organisms. Cancer cells in particular have high expression of Hsp90. Hsp90 has three structural domains including an N-terminal domain that contains an ATP binding site. Small molecule inhibitors of HSP90 (Hsp90i) can selectively and competitively to the Hsp90 ATP binding domain. HS-196 consists of a HSP90 inhibitor that binds competitively to the Hsp90 ATP binding domain connected by a linker to a contrast agent (near infrared (NIR) dye) that can be used for imaging. HS-196 can freely enter tumor cells to selectively bind Hsp90. Due to the the NIR dye, HS-196 accumulation in the malignant cells allows for specific visualization of tumors within the body.

HS-196 will be used in this investigation for the imaging of solid tumors The objectives of the study are to determine the dose of HS-196 that achieves the greatest ratio of tumor to normal tissue fluorescence in patients with malignancy, the safety of HS-196 administration in patients with malignancy, the average radiant efficiency in resected tumors following HS-196 administration, the localization of the HS-196 by microscopy of tumor slices, and the PK metrics of HS-196 when administered to patients.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase I Study of HS-196, an HSP90 Inhibitor-linked Near Infrared Probe for Detection of Solid Malignancies
Actual Study Start Date : August 10, 2018
Estimated Primary Completion Date : December 10, 2020
Estimated Study Completion Date : July 10, 2022

Arm Intervention/treatment
Experimental: HS-196
HS-196 will be administered intravenously as a single dose
Drug: HS-196
HS-196 will be administered intravenously as a single dose




Primary Outcome Measures :
  1. Fluorescence [ Time Frame: 1 day ]
    Ratio of tumor to normal tissue fluorescence


Secondary Outcome Measures :
  1. Number of AEs [ Time Frame: 1 month ]
    Safety of HS-196 administration in patients with malignancy

  2. Radiant Efficiency [ Time Frame: 1 day ]
    The average radiant efficiency in resected tumors following HS-196 administration.

  3. HS-196 Localization [ Time Frame: 1 day ]
    Localization of the HS-196 by microscopy of tumor slices.

  4. Maximum Plasma concentration Cmax [ Time Frame: 1 week ]
    PK metrics of HS-196 when administered IV to patients

  5. Area Under the Curve AUC [ Time Frame: 1 week ]
    PK metrics of HS-196 when administered IV to patients



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

For Dose escalation and recommended dose phases:

  • Diagnosis of a solid malignancy, stage I-IV, with planned surgical resection or biopsy.

For Expansion phase:

  • Patients with mammographically detected breast nodules with planned surgical resection or biopsy.

For All phases:

  • ECOG 0 or 1
  • Estimated life expectancy > 3 months
  • Age ≥ 18 years
  • Adequate hematologic function, with WBC ≥ 3000/microliter, hemoglobin ≥ 9 g/dL (it is acceptable to have had prior transfusion), platelets ≥ 75,000/microliter; PT-INR <1.5, PTT <1.5X ULN
  • Adequate renal and hepatic function, with serum creatinine < 1.5 mg/dL, bilirubin < 1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL), ALT and AST ≤ 2.5 x upper limit of normal or if liver metastases are present < 5 x upper limit of normal.
  • Female patients must be of non-child-bearing potential or use effective contraception, e.g., use of oral contraceptives with an additional barrier method (since the study drug may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, total abstinence, and willing to continue the effective contraception method for 30 days after the last dose of study drug;
  • Ability to understand and provide signed informed consent that fulfills Institutional Review Board's guidelines.
  • Ability to return to Duke University Medical Center for adequate follow-up, as required by this protocol.

Exclusion Criteria:

  • Serious chronic or acute illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment.
  • Medical or psychological impediment to probable compliance with the protocol.
  • Asthma under medical management
  • Uncontrolled high blood pressure
  • Presence of a known active acute or chronic infection including HIV or viral hepatitis (Hepatitis B and C)).
  • Pregnant or nursing women

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): NCT03333031


Contacts
Layout table for location contacts
Contact: Michael Morse, MD 919 684 5705 michael.morse@duke.edu
Contact: Amy Hobeika 919 684 6112 AMY.HOBEIKA@DUKE.EDU

Locations
Layout table for location information
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Michael Morse, MD    919-684-5705    michael.morse@duke.edu   
Sponsors and Collaborators
Herbert Lyerly
Investigators
Layout table for investigator information
Principal Investigator: H. Kim Lyerly, MD Duke University

Layout table for additonal information
Responsible Party: Herbert Lyerly, Professor, Duke University
ClinicalTrials.gov Identifier: NCT03333031    
Other Study ID Numbers: Pro00082272
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: September 23, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Herbert Lyerly, Duke University:
cancer
imaging agent
HSP90
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms