A Clinical Study to Determine the Pharmacokinetics of Oraxol in Breast Cancer Patients

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03165955

Enrollment

Registered

2017-05-24

Start date

2017-05-09

Completion date

2018-11-22

Last updated

2025-03-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breastcancer

Keywords

breast cancer, paclitaxel

Brief summary

This is a multicenter, open-label, single-arm PK study in patients for whom paclitaxel treatment is indicated.

Detailed description

This is a multicenter, open-label, single-arm PK study in approximately 24 breast cancer patients for whom paclitaxel treatment is indicated. The study contains 3 periods: the Screening / Baseline Period, the Treatment Period, and the Follow-up Period. A Final Visit will occur within 7 days of the last dose of study treatment. If subjects achieve stable disease (SD), partial response (PR), or complete response (CR) at the end of the Treatment Period, they may continue Oraxol treatment in a separate extension study.

Interventions

DRUGOraxol

HM30181 methanesulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets, Paclitaxel - supplied as 30-mg capsules

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Signed written informed consent 2. Women ≥18 years of age on day of consent 3. Breast cancer in patients for whom treatment with IV paclitaxel at 80 mg/m2 as monotherapy has been recommended by their oncologist 4. Measurable disease as per RECIST v1.1 criteria 5. Adequate hematological status as demonstrated by not requiring transfusion support or granulocyte-colony stimulating factor (G-CSF) maintain: * Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L * Platelet count ≥100 x 10\^9/L * Hemoglobin (Hgb) ≥9 g/dL 6. Adequate liver function * Total bilirubin of ≤1.5 mg/dL * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) or ≤5 x ULN if liver metastasis is present * Alkaline phosphatase (ALP) ≤3 x ULN or ≤5 x ULN if bone metastasis is present * Gamma glutamyl transferase (GGT) \<10 x ULN 7. Adequate renal function as demonstrated by serum creatinine ≤1.5 x ULN 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 9. Life expectancy of at least 3 months 10. Willing to fast for 6 hours before and 2 hours after Oraxol administration on all treatment days 11. Willing to abstain from alcohol consumption for 3 days before the first dose of study drug through the completion of the second inpatient PK sampling period 12. Willing to refrain from caffeine consumption for 12 hours before each inpatient dosing period through the completion of protocol-specified PK sampling for that week 13. Subjects must be postmenopausal (\>12 months without menses) or surgically sterile (ie, by hysterectomy and/or bilateral oophorectomy) or must be using effective contraception (ie, oral contraceptives, intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for 30 days after their last dose of assigned study treatment. 14. Subjects who are of childbearing potential must have a negative serum pregnancy test at Screening and within 96 hours before dosing.

Exclusion criteria

1. Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous investigational products (IPs) 2. If previously treated with a taxane (paclitaxel or docetaxel) as part of anthracycline-based adjuvant chemotherapy or for metastatic disease, the subject relapsed less than 1 year following treatment 3. Subjects unable to swallow study medication in its intact form or have clinically significant malabsorption syndrome 4. Only site of metastatic disease is unmeasurable according to RECIST v1.1 criteria 5. Known CNS metastasis, including leptomeningeal involvement 6. Received IPs within 14 days or 5 half-lives of the first study dosing day, whichever is longer 7. Are currently receiving other medications intended for the treatment of their malignancy 8. Women who are pregnant or breastfeeding 9. Taking prohibited medications: 10. Use of warfarin. Subjects receiving warfarin who are otherwise eligible and who may be appropriately managed with low molecular weight heparin, in the opinion of the Investigator, may be enrolled in the study provided they are switched to low molecular weight heparin at least 7 days prior to receiving study treatment. 11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia, chronic pulmonary disease requiring oxygen, known bleeding disorders, or any concomitant illness or social situation that would limit compliance with study requirements 12. Known allergic reaction or intolerance to study medication components 13. Known allergic reaction or intolerance to contrast media 14. Subjects who, in the Investigator's opinion, are not suitable for participation in this study

Design outcomes

Primary

Measure	Time frame	Description
PK Parameters for paclitaxel_tmax(48-52)	PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4	PK parameters were summarized using the median, minimum, maximum
PK Parameters for paclitaxel_Cmax(0-24)	PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4	PK parameters were summarized using the mean, SD
PK Parameters for paclitaxel_Cmax(24-48)	PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4	PK parameters were summarized using the mean, SD
PK Parameters for paclitaxel_Cmax(48-52)	PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4	PK parameters were summarized using the mean, SD
PK Parameters for paclitaxel_tmax(0-24)	PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4	PK parameters were summarized using the median, minimum, maximum
PK Parameters for paclitaxel_tmax(24-48)	PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4	PK parameters were summarized using the median, minimum, maximum
PK Parameters for paclitaxel_AUC (0-52)	PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4	PK parameters were summarized using the mean, SD
PK Parameters for paclitaxel_Cmax	PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4	PK parameters were summarized using the mean, SD
PK Parameters for paclitaxel_Ctrough(24)	PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4	PK parameters were summarized using the mean, SD
PK Parameters for paclitaxel_Ctrough(48)	PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4	PK parameters were summarized using the mean, SD

Secondary

Measure	Time frame	Description
Response Rate	From baseline through study completion, around 21 weeks	Tumor response rate and 95% confidence interval (CI) were evaluated based on the number of subjects with any post-baseline CR or PR per RECIST 1.1 as assessed by the Investigator and the ICRRC.
Progression-free Survival	From baseline through study completion, around 21 weeks	PFS was analyzed based on the Response Evaluable Population. The Kaplan-Meier (KM) method was used to estimate the medians of these variables with 95% CIs. The Response Evaluable Population included all subjects who received at least 1 dose of study treatment and had at least 1 posttreatment tumor response evaluation
Overall Survival	From baseline through study completion, around 21 weeks	OS was analyzed based on the Response Evaluable Population. The Kaplan-Meier (KM) method was used to estimate the medians of these variables with 95% CIs. The Response Evaluable Population included all subjects who received at least 1 dose of study treatment and had at least 1 posttreatment tumor response evaluation
Safety of Oraxol in Breast Cancer Patients	From enrollment through study completion, approximately 17 weeks	Safety was assessed by evaluating treatment-emergent adverse events (TEAEs) including SAEs, laboratory evaluations (hematology, blood chemistry, and urinalysis), vital signs, physical examinations, and electrocardiograms (ECGs).

Countries

Taiwan

Participant flow

Pre-assignment details

A total of 31 subjects were screened; 3 subjects were screen failures and were not included in the analysis

Participants by arm

Arm	Count
Oraxol (Oral Paclitaxel Plus HM30181) Oraxol 205 mg/m2 daily x 3 days weekly for up to 16 weeks.	28
Total	28

Withdrawals & dropouts

Period	Reason	FG000
Treatment	Adverse Event	1
Treatment	Death	1
Treatment	Progressive disease	3
Treatment	Withdrawal by Subject	3

Baseline characteristics

Characteristic	Oraxol (Oral Paclitaxel Plus HM30181)
Age, Continuous	56.6 years STANDARD_DEVIATION 9.04
ECOG 0	24 Participants
ECOG 1	4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	28 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment Taiwan	28 participants
Sex: Female, Male Female	28 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 28
other Total, other adverse events	27 / 28
serious Total, serious adverse events	8 / 28

Outcome results

Primary

PK Parameters for paclitaxel_AUC (0-52)

PK parameters were summarized using the mean, SD

Time frame: PK sampling timepoints: predose, and at 1, 2, 3, and 4 hours after dosing of Day 1, 2, 3 at Week 1 and 4