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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04035473




Registration number
NCT04035473
Ethics application status
Date submitted
14/06/2019
Date registered
29/07/2019
Date last updated
13/04/2022

Titles & IDs
Public title
A Study to Determine the Bioequivalence of Oraxol in Cancer Patients Treated With Intravenous Paclitaxel
Scientific title
A Randomized Crossover Study to Determine the Bioequivalence of Three Consecutive Daily Doses of Oraxol in Cancer Patients Treated With Intravenous Paclitaxel
Secondary ID [1] 0 0
KX-ORAX-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HM30181 methanesulfonate monohydrate plus oral paclitaxel capsules

Active Comparator: Sequence A (Oraxol, IV paclitaxel) - The treatment sequences will be:
A Oraxol (paclitaxel + HM30181) on Days 1, 2, and 3 of Treatment Period 1 followed by IV paclitaxel on Day 1 of Treatment Period 2 B IV paclitaxel on Day 1 of Treatment Period 1 followed by Oraxol on Days 1, 2, and 3 of Treatment Period 2

Active Comparator: Sequence B (IV paclitaxel, Oraxol) - The treatment sequences will be:
A IV paclitaxel on Day 1 of Treatment Period 1 followed by Oraxol on Days 1, 2, and 3 of Treatment Period 2 B Oraxol (paclitaxel + HM30181) on Days 1, 2, and 3 of Treatment Period 1 followed by IV paclitaxel on Day 1 of Treatment Period 2


Treatment: Drugs: HM30181 methanesulfonate monohydrate plus oral paclitaxel capsules
HM30181 methanesulfonate monohydrate plus oral paclitaxel capsules
Oral paclitaxel capsules
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Concentration-Time Curve Zero Time Extrapolated to Infinite Time (AUC0-8)
Timepoint [1] 0 0
Pharmacokinetic Sampling for IV Paclitaxel - Predose to 96 hours after infusion (Day 1-5). Pharmacokinetic Sampling for Oraxol- predose of Day1 to 144 hours after third dose of day 3 (Day 1-9)
Secondary outcome [1] 0 0
Maximum Observed Concentration (Cmax)
Timepoint [1] 0 0
Pharmacokinetic Sampling for IV Paclitaxel - Predose to 96 hours after infusion (Day 1-5). Pharmacokinetic Sampling for Oraxol- predose of Day1 to 144 hours after third dose of day 3 (Day 1-9)
Secondary outcome [2] 0 0
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t)
Timepoint [2] 0 0
Pharmacokinetic Sampling for IV Paclitaxel - Predose to 96 hours after infusion (Day 1-5). Pharmacokinetic Sampling for Oraxol- predose of Day1 to 144 hours after third dose of day 3 (Day 1-9)
Secondary outcome [3] 0 0
Time at Which the Highest Drug Concentration Occurs (Tmax)
Timepoint [3] 0 0
Pharmacokinetic Sampling for IV Paclitaxel - Predose to 96 hours after infusion (Day 1-5). Pharmacokinetic Sampling for Oraxol- predose of Day1 to 144 hours after third dose of day 3 (Day 1-9)
Secondary outcome [4] 0 0
Terminal Elimination Phase Half-life (t½)
Timepoint [4] 0 0
Pharmacokinetic Sampling for IV Paclitaxel - Predose to 96 hours after infusion (Day 1-5). Pharmacokinetic Sampling for Oraxol- predose of Day1 to 144 hours after third dose of day 3 (Day 1-9)
Secondary outcome [5] 0 0
Safety and Tolerability of Oraxol Compared With IV Paclitaxel
Timepoint [5] 0 0
From screening until final visit (within 28 days after the last dose of study drug was taken, and preferably before the participant receives any additional chemotherapy)

Eligibility
Key inclusion criteria
1. Signed written informed consent

2. Males and females =18 years of age on day of consent

3. Cancer patients for whom treatment with IV paclitaxel at 80 mg/m2has been recommended
by their oncologist, either as monotherapy or in combination with other agents

4. Adequate hematologic status at Screening/Baseline:

- Absolute neutrophil count (ANC) =1.5 x 109/L

- Platelet count =100 x 109/L

- Hemoglobin (Hgb) =90 g/L

5. Adequate liver function at Screening/Baseline as demonstrated by:

- Total bilirubin of =20 µmol/L or =30 µmol/L for participants with liver
metastasis

- Alanine aminotransferase (ALT) =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 liver or bone metastasis are
present

- ALP >5 x ULN if liver or bone metastasis are present and the major fraction of
ALP is from bone metastasis, at the discretion of the Investigator

- Gamma glutamyl transferase (GGT) <10 x ULN

6. Adequate renal function at Screening/Baseline as demonstrated by serum creatinine =177
µmol/L or creatinine clearance >50 mL/min as calculated by the Cockcroft and Gault
formula

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 16

8. Life expectancy of at least 3 months

9. Willing to fast for 8 hours before and 4 hours after Oraxol administration

10. Willing to abstain from alcohol consumption for 3 days before the first dose of study
drug through the completion of protocol-specified PK sampling in Treatment Period 2

11. Willing to refrain from caffeine consumption for 12 hours before each treatment period
through the completion of protocol-specified PK sampling for that dose

12. Women must be postmenopausal (>12 months without menses) or surgically sterile (ie, by
hysterectomy and/or bilateral oophorectomy) or, if sexually active, 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 the
duration of their participation in the study. Women of childbearing potential must
agree to use contraception for 30 days after their last dose of study drug.

13. Sexually active male participants must use a barrier method of contraception during
the study and agree to continue the use of male contraception for at least 30 days
after the last dose of study drug.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Currently taking a prohibited concomitant medication:

- Strong inhibitors (eg, ketoconazole) or strong inducers (eg, rifampin or St.
John's Wort) of cytochrome P450 (CYP) 3A4 (within 2 weeks prior to the start of
dosing in the study)

- Strong inhibitors (eg, gemfibrozil) or strong inducers (eg, rifampin) of CYP2C8
(within 2 weeks prior to the start of dosing in the study)

- Known P-glycoprotein (P-gp) inhibitors or inducers. Participants who are taking
such medications but who are otherwise eligible may be enrolled if they
discontinue the medication =1 week before dosing and remain off that medication
through the end of PK sampling after the administration of the second study
treatment.

- An oral medication with a narrow therapeutic index known to be a P-gp substrate
(eg, digoxin, dabigatran) within 24 hours prior to start of dosing in the study

2. Use of warfarin. Participants 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.

3. Unresolved toxicity from prior chemotherapy (participants must have recovered all
significant toxicity to = Grade 1 CTCAE toxicity1 from previous anticancer treatments
or previous investigational agents). This does not extend to symptoms or findings that
are attributable to the underlying disease

4. Received investigational agents within 14 days or 5 half-lives prior to the first
study dosing day, whichever is longer

5. Women of childbearing potential who are pregnant or breastfeeding

6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, clinically significant myocardial
infarction within the last 6 months, unstable angina pectoris, clinically significant
cardiac arrhythmia, bleeding disorder, chronic pulmonary disease requiring oxygen, or
psychiatric illness/social situations that would limit compliance with study
requirements

7. Major surgery to the upper GI tract, or have a history of GI disease or other medical
condition that, in the opinion of the Investigator may interfere with oral drug
absorption

8. A known history of allergy to paclitaxel. Participants whose allergy was due to the IV
solvent (such as Cremophor®) and not paclitaxel will be eligible for this study.

9. Any other condition which the Investigator believes would make a subject's
participation in the study not acceptable

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/03/2019
Sample size
Target
Accrual to date
Final
42
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Monash Medical Centre - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Dunedin
Country [3] 0 0
New Zealand
State/province [3] 0 0
Wellington
Country [4] 0 0
Taiwan
State/province [4] 0 0
Ilan
Country [5] 0 0
Taiwan
State/province [5] 0 0
New Taipei City
Country [6] 0 0
Taiwan
State/province [6] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Athenex, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
PharmaEssentia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Zenith Technology Corporation Limited
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicenter, open-label, 2-stage study with a 2-treatment period crossover design.
Eligible participants are adults with cancer for whom weekly therapy with IV paclitaxel at a
dose of 80 mg/m2 over 1 hour is indicated.

Stage 1 will consist of an initial cohort (Cohort 1) up to 6 evaluable participants who will
receive a dosing regimen of Oraxol consisting of a 15-mg oral HM30181AK-US tablet plus an
oral paclitaxel dose of 205 mg/m2, both administered once daily for 3 consecutive days. The
stages and cohorts are further described in the "Study Design - Stages and Cohorts" table
below. An interim analysis of pharmacokinetic (PK) data from Cohort 1 will be conducted to
determine if the administered regimen would appear likely to achieve bioequivalence(BE)
(AUC0-8), if tested in a greater number of participants in Stage 2. If it appears unlikely
that the selected regimen will meet the criteria for BE based on AUC0-8 data, a second cohort
(Cohort 2) of up to 6 evaluable participants may be enrolled in Stage 1, and the dose of
paclitaxel in Oraxol may be adjusted by a maximum of +/- 25%. If Cohort 2 is enrolled, a
second interim analysis will be conducted.

After the interim analysis/analyses (depending on the outcomes), a decision will be made by
consensus of the Data Safety and Monitoring Board(DSMB), Kinex, Zenith Technology, and the
Principal Investigator as to what dose should be administered in Stage 2. The DSMB will
consist of a clinical oncologist, an ethicist, an independent statistician, and additional
members, as deemed necessary. A DSMB charter will describe the planned evaluations and
decision points used to determine the dose for Stage 2. An additional 18 to 42 evaluable
participants will be enrolled into Stage 2 based on the Stage 1 results (AUC0-8). Thus a
total of up to 54 evaluable participants could potentially be enrolled in this study (6 each
from Stage 1, Cohorts 1 and 2, and up to 42 participants in Stage 2).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04035473
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Cutler, MD
Address 0 0
Athenex, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04035473