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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/NCT04180384




Registration number
NCT04180384
Ethics application status
Date submitted
13/06/2019
Date registered
27/11/2019
Date last updated
29/07/2021

Titles & IDs
Public title
A Safety Study of Oraxol (HM30181 + Oral Paclitaxel) in Cancer Patients
Scientific title
A Safety Study of Oraxol (HM30181 + Oral Paclitaxel) in Cancer Patients
Secondary ID [1] 0 0
KX-ORAX-003
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 - Oraxol

Experimental: Oraxol (paclitaxel capsules+ HM30181AK-US) - Oraxol paclitaxel - supplied as 30-mg capsules
Oraxol HM30181 methansulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets

Active Comparator: Oraxol (paclitaxel tablets+ HM30181AK-US) - Oraxol paclitaxel - supplied as 30-mg tablets
Oraxol HM30181 methansulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets


Treatment: Drugs: Oraxol
Paclitaxel:
5ß,20-Epoxy-1,2a,4,7ß,10ß,13a-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13- ester with (2R,3S)-N-benzoyl-3-phenylisoserine
HM30181 methanesulfonate monohydrate:
N-(2-(2-(4-(2-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-2H-tetrazol-5-yl)-4,5-dimethoxyphenyl)-4-oxo-4H-chromene-2-carboxamide Methanesulfonate monohydrate
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability of Oraxol (Incidence of Treatment-Emergent Adverse Events)
Timepoint [1] 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).
Secondary outcome [1] 0 0
Sustained oral bioavailability of paclitaxel following multiple dosing
Timepoint [1] 0 0
PK samples will be collected during dosing for Week 4 or may be done during a later dosing week at the investigator's discretion and/or at the participant's convenience before patients' withdrawal from the study, up to 8 months.
Secondary outcome [2] 0 0
the relative bioavailability of paclitaxel tablets vs paclitaxel capsules (Group B only)
Timepoint [2] 0 0
PK samples will be collected during dosing for Week 5; or may be done during a later dosing week at the investigator's discretion and/or at the participant's convenience, up to 8 months.

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/m2 has been recommended
by their oncologist, either as monotherapy or in combination with other agents

4. Adequate hematologic status:

- Absolute neutrophil count (ANC) =1.5 x 10^9/L

- Platelet count =100 x 10^9/L

- Hemoglobin (Hgb) =90 g/L

5. Adequate liver function 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 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 on all
treatment days (but may have water 1 hour after completion of Oraxol dosing and as
needed with other prescribed medications)

10. During the inpatient PK sampling week(s):

- Willing to abstain from alcohol consumption for 3 days before the first dose of
Oraxol through the completion of protocol-specified PK sampling for that
treatment week

- Willing to refrain from caffeine consumption for 12 hours before the first dose
of Oraxol through the completion of protocol-specified PK sampling for that
treatment week

11. Women must be postmenopausal (>12 months without menses) or surgically sterile (ie, by
hysterectomy and/or bilateral oophorectomy) or, if of childbearing potential, 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 6 months after their last dose of study drug.

12. 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 6 months
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)

- Strong P-gp inhibitors (eg, verapamil) or strong inducers (eg, rifampin).
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 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 toxicity 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
Non-randomised 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
Factorial
Other design features
Phase
Phase 2
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
23/09/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/06/2021
Sample size
Target
Accrual to date
Final
44
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
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
New Taipei City
Country [5] 0 0
Taiwan
State/province [5] 0 0
Taipei
Country [6] 0 0
Taiwan
State/province [6] 0 0
Yilan
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Manchester

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
Zenith Technology Corporation Limited
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
PharmaEssentia
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Oraxol is a combination of an oral tablet, HM30181 methanesulfonate, and capsules that
contain paclitaxel. HM30181 is a drug that helps the body absorb paclitaxel, a drug used to
treat cancer. Initially this study is intended as an extension study of KX-ORAX-002
pharmacokinetic study for patients who wish to continue Oraxol treatment and who are eligible
to participate. The purpose of this study is to check the safety and tolerability of Oraxol
when it is administered on a weekly basis and to confirm the sustained oral bioavailability
of paclitaxel following multiple dosing; also compare the relative bioavailability of
paclitaxel tablets vs paclitaxel capsules (Group B only).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04180384
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jackson Christopher, MD
Address 0 0
Dunedin Hospital
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