NXP800 for the Treatment of Patients With Advanced or Metastatic Cholangiocarcinoma

NCT ID: NCT06420349

Last Updated: 2025-12-22

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

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-31

Study Completion Date

2025-09-09

Brief Summary

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This phase I trial tests the safety, best dose, and effectiveness of NXP800 in treating patients with cholangiocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). NXP800 inhibits a pathway called the heat shock factor 1 (HSF1) pathway. The inhibition of this pathway inhibits proliferation, migration, survival, and metastasis in susceptible tumor cells. Overexpressed, amplified and/or overactivated in many cancer cells, HSF1 activates a set of genes that play a key role in tumor initiation, progression and metastasis. Inhibiting this pathway may in turn inhibit tumor initiation, progression, and/or metastasis. Giving NXP800 may be safe, tolerable and/or effective in treating patients with advanced or metastatic cholangiocarcinoma.

Detailed Description

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PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD)/recommended phase 2 dose for heat shock factor 1 pathway inhibitor NXP800 (NXP800).

SECONDARY OBJECTIVES:

I. To determine the toxicity profile of NXP800. II. To determine the best response for NXP800 using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

III. To estimate the overall survival (OS) for NXP800. IV. To estimate the progression-free survival (PFS) for NXP800.

EXPLORATORY OBJECTIVES:

I. To evaluate transcriptomic features associated with sensitivity, resistance and pharmacodynamic effect of NXP800 using serial ribonucleic acid-sequencing (RNA-Seq).

II. To assess tumor evolution with NXP800 using serial whole genome-sequencing (Seq).

III. To assess tumor evolution with NXP800 using serial circulating tumor deoxyribonucleic acid (DNA) (ct-DNA).

IV. To estimate tumor marker response using serial CA19-9/carcinoembryonic antigen (CEA).

OUTLINE: This is a dose de-escalation study of NXP800 followed by a dose-expansion study.

Patients receive NXP800 orally (PO) according to assigned treatment schedule. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) at baseline and on study. Patients may optionally undergo ultrasound-guided tumor biopsy and/or collection of blood samples on study and during follow up.

After completion of study treatment, patients are followed up every 6 months until progressive disease or death for up to 3 years.

Conditions

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Advanced Cholangiocarcinoma Metastatic Cholangiocarcinoma Refractory Cholangiocarcinoma Stage III Hilar Cholangiocarcinoma AJCC v8 Stage III Intrahepatic Cholangiocarcinoma AJCC v8 Stage IV Hilar Cholangiocarcinoma AJCC v8 Stage IV Intrahepatic Cholangiocarcinoma AJCC v8

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (NXP800)

Patients receive NXP800 according to assigned treatment schedule. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or PET at baseline and on study. Patients may optionally undergo ultrasound-guided tumor biopsy and/or collection of blood samples on study and during follow up.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Heat Shock Factor 1 Pathway Inhibitor NXP800

Intervention Type BIOLOGICAL

Given PO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Ultrasound-Guided Biopsy

Intervention Type PROCEDURE

Undergo ultrasound-guided tumor biopsy

Interventions

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Biospecimen Collection

Undergo collection of blood samples

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Heat Shock Factor 1 Pathway Inhibitor NXP800

Given PO

Intervention Type BIOLOGICAL

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET

Intervention Type PROCEDURE

Ultrasound-Guided Biopsy

Undergo ultrasound-guided tumor biopsy

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography CCT 361814 CCT-361814 CCT361814 HSF1 Pathway Inhibitor NXP800 NXP-800 NXP800 VK2019 Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Ultrasound Biopsy Ultrasound Guided Biopsy

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years
* Histologically/cytologically confirmed biliary tract cancer
* Advanced or metastatic disease that is refractory to gemcitabine or fluoropyrimidine based therapy, or if there is intolerance to these regimens
* Measurable disease by RECIST 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Anticipated life expectancy of \> 12 weeks
* Hemoglobin ≥ 9.0 g/dL (obtained ≤ 14 days prior to registration)
* Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained ≤ 14 days prior to registration)
* Platelet count ≥ 100,000/mm\^3 (obtained ≤ 14 days prior to registration)
* Aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to registration)
* Alanine aminotransferase (ALT) ≤ 5 x ULN (obtained ≤ 14 days prior to registration)
* Total bilirubin ≤ 1.5 x ULN (obtained ≤ 14 days prior to registration)
* Serum creatinine ≤ 1.5 x ULN (obtained ≤ 14 days prior to registration)
* Provide written informed consent
* Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only

* NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Willing to use a highly effective method of contraception from the first dose of study medication through 180 days after the last dose of study medication, for persons of childbearing potential or persons able to father a child only
* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria

* Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:

* Pregnant persons.
* Nursing persons.
* Persons of childbearing potential who are unwilling to employ adequate contraception
* Systemic anti-neoplastic therapy or radiation therapy ≤ 14 days prior to registration
* Major surgical procedure ≤ 28 days prior to registration
* Ongoing therapy related events \> grade 2
* Presence of another primary malignancy not in remission
* New York Heart Classification 3 or greater heart failure
* QT/corrected QT (QTc) interval \> 470 ms using Fredericia's QT correction formula
* Uncontrolled brain metastatic disease
* Uncontrolled infection
* Any other comorbidities within the opinion of the investigator interfere with the investigation of the protocol
* Usage of drugs that strongly inhibit or induce CYP3A4 ≤ 7 days prior to registration and for the duration of NXP800 dosing. Drugs that are low, medium, or other inhibitors of CYP3A4 are not prohibited and should be used with caution. Drugs that inhibit BCRP are not prohibited but should be used with caution, since NXP800 was found to be a BCRP substrate
* Usage of seville oranges, grapefruit or grapefruit juice or products ≤ 7 days prior to registration and for the duration of NXP800 dosing
* Unwillingness to follow study related procedures
* Inability to provide informed consent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mitesh J. Borad, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Countries

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United States

References

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Kuipers H, Larson JJ, Conboy CB, Ahn DH, Bekaii-Saab T, Wu C, Sonbol MB, Ilyas SI, Gores GJ, Smoot RL, Borad MJ. A Phase 1 study of the novel GCN2 kinase activator NXP800 in patients with advanced cholangiocarcinoma. Future Oncol. 2025 Sep;21(21):2723-2730. doi: 10.1080/14796694.2025.2539611. Epub 2025 Jul 28.

Reference Type DERIVED
PMID: 40717483 (View on PubMed)

Related Links

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Other Identifiers

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NCI-2024-03613

Identifier Type: REGISTRY

Identifier Source: secondary_id

MC230406

Identifier Type: OTHER

Identifier Source: secondary_id

23-012778

Identifier Type: OTHER

Identifier Source: secondary_id

MC230406

Identifier Type: -

Identifier Source: org_study_id