Clinical trial NCT04046016: A Study Using Whole-body PET After Oral Microdose of 18F-labeled Liporaxel in Patients With Solid Tumor
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Solid Tumor
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2019-08-06
Enrollment: 2
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax
timeFrame: pre-dose, 2, 4, 6, 8, 10 hours after post-dose
measure: AUClast
timeFrame: pre-dose, 2, 4, 6, 8, 10 hours after post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyounggi
Study officials:
affiliation: Seoul National University Hospital
name: Howard Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: