HS-201, an HSP90 Inhibitor-linked Verteporfin for Detection of Solid Malignancies

NCT ID: NCT03906643

Last Updated: 2022-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-15

Study Completion Date

2023-02-20

Brief Summary

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HS-201 is Verteporfin-tethered HSP90 inhibitor for clinical imaging of selective tumor binding. HS-201 consists of a HSP90 inhibitor that binds competitively to the Hsp90 ATP binding domain connected by a linker to a photosensitizing agent (verteporfin) that can be used for imaging. HS-201 can freely enter tumor cells to selectively bind Hsp90. Due to the the verteporfin, HS-201 accumulation in the malignant cells allows for specific visualization of tumors within the body and verteporfin may allow for photodynamic therapy of tumors.

Detailed Description

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The product to be tested in this study, HS-201, 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 photosensitzing agent (verteporfin) that can be used for imaging. HS-201 can freely enter tumor cells to selectively bind Hsp90. Due to the verteporfine, HS-201 accumulation in the malignant cells allows for specific visualization of tumors within the body.

HS-201 will be used in this investigation for the imaging of solid tumors The objectives of the study are to determine the dose of HS-201 that achieves the greatest ratio of tumor to normal tissue fluorescence in patients with malignancy, the safety of HS-201 administration in patients with malignancy, the average radiant efficiency in resected tumors following HS-201 administration, the localization of the HS-201 by microscopy of tumor slices, and the PK metrics of HS-201 when administered to patients.

Conditions

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Solid Tumor

Keywords

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tumor verteporfin HSP90 inhibitor

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Open label phase I study
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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HS-201

HS-201 will be administered intravenously as a single dose

Group Type EXPERIMENTAL

HS-201

Intervention Type DRUG

HS-201 will be administered intravenously as a single dose

Interventions

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HS-201

HS-201 will be administered intravenously as a single dose

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of a solid malignancy, stage I-IV.
* Planned surgical resection or biopsy of a malignancy
* 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
* 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.
* Patients with porphyria or a known hypersensitivity to any component of this preparation are excluded.
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Herbert Lyerly

OTHER

Sponsor Role lead

Responsible Party

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Herbert Lyerly

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Duke University Medical Center

Durham, North Carolina, United States

Site Status

Countries

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United States

Other Identifiers

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Pro00102188

Identifier Type: -

Identifier Source: org_study_id