A Safety Study of Oraxol (HM30181 + oral paclitaxel) in Cancer Patients

• Register: ANZCTR
• Last refreshed on: 1 November 2021
• Main ID: ACTRN12615000881538
• Date of registration: 24/08/2015
• Prospective Registration: Yes
• Primary sponsor: Kinex Pharmaceuticals Inc
• 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
• Date of first enrolment: 16/09/2015
• Target sample size: 44
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12615000881538.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety;
• Phase: Phase 2

Countries of recruitment

Australia, New Zealand, Taiwan, Province Of China, United Kingdom

Contacts

• Name: Dr E. Douglas Kramer

• Name: Mrs Linda Folland

Key inclusion & exclusion criteria

Inclusion criteria: Eligible participants are 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.
At Screening/Baseline, they must have
Adequate hematologic status:
- Absolute neutrophil count (ANC) greater than/equal to 1.0 x 10^9/L
- Platelet count greater than/equal to 100 x 10^9/L
- Hemoglobin greater than/equal to 90g/L
Adequate liver function as demonstrated by:
- Total bilirubin of less than/equal to 20 micromol/L or less than/equal to 30 µmol/L for participants with liver metastasis
Alanine aminotransferase (ALT) less than/equal to 3 x upper limit of normal (ULN) or less than/equal to 5 x ULN if liver metastasis is present
Alkaline phosphatase (ALP) less than/equal to 3 x ULN or less than/equal to 5 x ULN if liver or bone metastasis is present
Adequate renal function as demonstrated by serum creatinine less than/equal to 177 micromol/L or creatinine clearance greater than 50 mL/min as calculated by the Cockroft and Gault formula.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; and life expectancy of at least 3 months.
They must be willing to fast for 8 hours before and 4 hours after Oraxol administration; 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. Women must be postmenopausal (more than 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. 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.
Exclusion criteria: Study participants must not be:
Currently taking a prohibited concomitant medication;
- a medication known to be a P-gp inhibitor (e.g., verapamil) or inducer (rifampin) within 7 days prior to the first dose of Oraxol
- an oral medication with a narrow therapeutic index known to be a P-gp substrate (eg, digoxin or dabigatran) within 24 hours prior to the first dose of Oraxol
- a medication known to be a strong CYP3A4 strong inhibitor (e.g., ketoconazole) or strong inducer (e.g., rifampin or St. John's Wort) within 14 days prior to the first dose of Oraxol
- a medication known to be a strong inhibitor (e.g., gemfibrozil) or inducers (e.g., rifampin) of CYP2C8 within 14 days prior to the first dose of Oraxol

Other exclusions are: unresolved toxicity from prior chemotherapy;
have received investigational agents within 14 days or 5 half-lives prior to the first study dosing day, whichever is longer. Other exclusions are women of childbearing potential who are pregnant or breast feeding; uncontrolled intercurrent illness; major surgery to the upper gastrointestinal 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; known history of allergy to paclitaxel (Participants whose allergy was due to the IV solvent (such as Cremophor [Registered Trademark]) and not paclitaxel will be eligible for this study); any other condition which the investigator believes would make a subject’s participation in the study not acceptable.

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Cancer requiring treatment with IV paclitaxel;
Cancer requiring treatment with IV paclitaxel

Cancer - Any cancer

Intervention(s)

Approximately 40 participants will be treated with a daily dosage regimen of Oraxol 205 mg/m2 on Days 1, 2, and 3 every week (i.e. a total Oraxol dose of 615mg/m2 over three days of dosing), or as adjusted in KX-ORAX-002 to achieve bioequivalence to IV paclitaxel 80 mg/m2 infused over 1 hour. Oraxol will be administered once daily for 3 consecutive days on a weekly basis as 15 mg oral HM30181AK-US tablet plus oral paclitaxel capsules. Oral paclitaxel capsules are administered one hour after the HM30181AK-US tablet. Participants must fast for 8 hours prior to administration of Oraxol and for four hours afterwards. Participants will be asked to return their daily Oraxol dose cards to check for compliance. Doses during the PK sampling week (Week 4 or later) will be administered at the study site.
A subgroup of participants (Group B) will also receive one dose of Oraxol where paclitaxel is administered as tablets rather than as capsules for one week only.
Participants may enter this study after completion of a previous study involving Oraxol (KX-ORAX-002). The study procedures are the same regardless of whether a participant was in the previous study or not; however some data (e.g. medical history) collected for the previous study would not need to be collected again for this study. The dose and administartion of Oraxol to be used in this study will be the same as the dose in the previous study that is confirmed to be equivalent to the administration of IV Paclitaxel at 80mg/m2.
Participants may continue to receive treatment with Oraxol (HM30181AK-US tablet and paclitaxel capsules) in this study until any of the following occur: death, successful completion of the course of treatment prescribed by the investigator, progression of disease, AEs not associated with pr

Primary Outcome(s)

Safety and tolerability as assessed by the results of routine laboratory safety tests (i.e. haematology, biochemistry and urinalysis).[At screening/baseline, weekly (within 72hrs prior to the start of dosing each week), and at the final visit (within 28 days after the last dose of study drug was taken, and preferably before the participant receives any additional chemotherapy). Long-term patients may have the frequency of routine laboratory safety tests reduced to every three weeks after Week 48]

Safety and tolerability as assessed by the severity and relationship of adverse events. Treatment-emergent AEs (TEAEs) are defined as those AEs with an onset after dosing and those pre-existing AEs that worsen during the study. [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).]

Safety and tolerability as assessed by the incidence of adverse events. Treatment-emergent AEs (TEAEs) are defined as those AEs with an onset after dosing and those pre-existing AEs that worsen during the study.
AEs will include those reported by participants as well as those observed by the clinical team, or clinically significant changes in lab tests, vital signs and ECGs. Possible AEs may include gastrointestinal effects and abdominal pain but as this is an early phase clinical trial and the likely AE profile is not yet known.[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(s)

Oraxol PK data from this study will be compared with Oraxol PK data from study KX-ORAX-002. The PK parameters to be used are AUCs, clearance, Cmax and Tmax.[From pre-dose until 8 hours post-dose on Days 1, 2 and 3. This time period is shorter to the time period used in the KX-ORAX-002 study, where PK blood samples are being collected until 144 hours post-dose on Day 3. 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. ]

Safety as assessed by vital signs. Vital signs include pulse rate, systolic/diastolic blood pressure, respiratory rate, and temperature. [Vital signs are measured at Screening/Baseline, before dosing on Day 1 of every 3rd week (Weeks 1, 4, 7, 10, etc), and before dosing during the inpatient dosing week and at the Final Visit (within 28 days after the last dose of study drug was taken, and preferably before the participant receives any additional chemotherapy).]

Safety as assessed by Physical Examinations. A complete PE will include an assessment of HEENT, gastrointestinal, cardiovascular, respiratory, integumentary, muscular- skeleton, neurological and endocrine/metabolism systems. Complete PEs will be performed at Screening/Baseline and at the Final Visit. All other physical examinations do not require complete examinations but will be targeted to the signs and symptoms related to Adverse Event Reporting. Additional examinations will be performed as clinically indicated to assess adverse events.[At screening/baseline, Weeks 1, 4, 7 10 etc, and at the final visit (within 28 days after the last dose of study drug was taken, and preferably before the participant receives any additional chemotherapy). ]

Safety as assessed by the use of concomitant medications, as recorded in their clinical notes and reported by participant's during their weekly contact with the study site.[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).]

Safety, as assessed by ECGs.[At screening/baseline, Weeks 1, 4, 13 and 20, and at the final visit (within 28 days after the last dose of study drug was taken, and preferably before the participant receives any additional chemotherapy). ]

Safety as assessed by Eastern Co-operative Oncology Group (ECOG) performance status.[At screening/baseline, Weeks 1, 4, 7 10 etc, and at the final visit (within 28 days after the last dose of study drug was taken, and preferably before the participant receives any additional chemotherapy). ]

To compare the relative bioavailability of paclitaxel tablets vs paclitaxel capsules (Group B only)[Pre-dose, then hours 1, 2, 3, 4, 6 and 8 hours post-dose on Days 1, 2 and 3. This time period is shorter to the time period used in the KX-ORAX-002 study, where PK blood samples are being collected until 144 hours post-dose on Day 3. 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. ]

Secondary ID(s)

KX-ORAX-003

Source(s) of Monetary Support

Kinex Pharmaceuticals Inc

Secondary Sponsor(s)

Zenith Technology Corporation Ltd.

Ethics review

Status: Approved
Approval date: 24/06/2015
Contact:

Southern Health and Disability Ethics Committee

Results

• Results available: Yes
• Date Posted: 31/05/2019
• Date Completed: 15/06/2021