A Study Using Whole-body PET After Oral Microdose of 18F-labeled Liporaxel in Patients With Solid Tumor

A Phase 0 Study to Investigate Biodistribution and Target Tissue Distribution Using Whole-body PET Scan After Oral Administration of Therapeutic Dose of Liporaxel Solution and Microdose of 18F-labeled Liporaxel in Patients With Solid Tumor

An open-label, single oral dose of therapeutic Liporaxel and microdose 18F-Liporaxel administration study was conducted in two breast cancer patients. Therapeutic dose of Liporaxel was 200 mg/m2 and 18F-Liporaxel was 0.98-2.9 μg (185-555 MBq).

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Paclitaxel

Detailed Description

The subject should be diagnosed as solid cancer on histopathology or cytology and should be more than 19 years old. Patients with progressed, metastatic, or recurrent disease despite standard therapies for solid tumors were included. The disease had to be measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The Eastern Cooperative Oncology Group (ECOG) performance status should be less than 2 and the predicted survival time should be more than 12 weeks. Those who were not able to take the oral medication or who had an operation that could lead to abnormal bile acid secretion were excluded. Patients with a history of adverse reactions and allergic reactions to paclitaxel or paclitaxel-like substances (e.g., taxol) were also excluded. Patients who are taking P-glycoprotein inducers or inhibitors or drugs which is known to exist drug-drug interaction with paclitaxel (e.g., cyclosporine A, ketoconazole, rifampicin, clarithromycin) were excluded. Patients with a neutrophil count less than 1,500 cell/mm3, platelet count less than 100,000 cells/mm3, and with infectious diseases at the beginning of the study were excluded.

Subjects eligible for the inclusion/exclusion criteria were orally administered Liporaxel solution 300 mg containing a microdose amount of 18F-Liporaxel on Visit 1. At 0, 2, 4, 8, 10 h post-dose, whole body PET/CT imaging (head-to-thigh) were obtained. Visit 2, 3, and 4 were taken 1, 2, and 3 weeks after Visit 1, respectively. For each visit, the adverse events, vital sign, physical examination, and clinical laboratory test results were evaluated and then therapeutic dose of Liporaxel was administered. Five weeks after Visit 1, the subject self-administered Liporaxel and adverse events and comedication were followed up by phone. At Visit 6, eight weeks after Visit 1, RECIST measurements were made with contrast-enhanced CT with safety evaluation. Tumor response was assessed to determine whether the study could be completed. If the tumor response was progression, the study was to be terminated. If stable disease, subject started a new cycle starting from Visit 6, and decided to evaluate tumor response with CT scan every eight week based on Visit 6. If the subject did not adequately recover from the hematologic and non-hematologic toxicities of Liporaxel during the entire study, the doses could be delated for up to two weeks at the discretion of the investigator. Exclusion was made in cases exceeding two weeks.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyounggi
    • Seongnam, Gyounggi, Korea, Republic of
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. The subject should be diagnosed as solid cancer on histopathology or cytology and should be more than 19 years old.
2. Patients with progressed, metastatic, or recurrent disease despite standard therapies for solid tumors were included.
3. The disease had to be measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
4. The Eastern Cooperative Oncology Group (ECOG) performance status should be less than 2 and the predicted survival time should be more than 12 weeks.

Exclusion criteria:

1. Those who were not able to take the oral medication or who had an operation that could lead to abnormal bile acid secretion were excluded.
2. Patients with a history of adverse reactions and allergic reactions to paclitaxel or paclitaxel-like substances (e.g., taxol) were also excluded.
3. Patients who are taking P-glycoprotein inducers or inhibitors or drugs which is known to exist drug-drug interaction with paclitaxel (e.g., cyclosporine A, ketoconazole, rifampicin, clarithromycin) were excluded.
4. Patients with a neutrophil count less than 1,500 cell/mm3, platelet count less than 100,000 cells/mm3, and with infectious diseases at the beginning of the study were excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects; A total of two subjects were enrolled. Those are breast cancer patients.	Drug: Paclitaxel; Liporaxel and microdose 18F-Liporaxel administration study was conducted in two breast cancer patients. Therapeutic dose of Liporaxel was 200 mg/m2 and 18F-Liporaxel was 0.98-2.9 μg (185-555 MBq).; Other Names: Liporaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Plasma paclitaxel peak concentration	pre-dose, 2, 4, 6, 8, 10 hours after post-dose
AUClast	Plasma paclitaxel area under the time-concentration curve until the last measurable time point	pre-dose, 2, 4, 6, 8, 10 hours after post-dose

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Howard Lee, MD, PhD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2018
• Primary Completion (Actual): December 24, 2018
• Study Completion (Actual): December 24, 2018

Study Registration Dates

• First Submitted: May 17, 2019
• First Submitted That Met QC Criteria: August 4, 2019
• First Posted (Actual): August 6, 2019

Study Record Updates

• Last Update Posted (Actual): August 6, 2019
• Last Update Submitted That Met QC Criteria: August 4, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: DHP107_Bioimaging

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No