None listed
Conditions
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. The purpose of this study is to measure the levels of paclitaxel in your blood at different times when given by intravenous (IV) drip (through a vein in the arm) compared to the levels of paclitaxel at different times in the blood when given by mouth (as Oraxol). This is called pharmacokinetic or “PK” testing
Interventions
Crossover Design:
Study treatments will be administered on consecutive weeks with 1 week between each treatment administration.
There are two sequences; IV paclitaxel followed by 15 mg oral HM30181 methanesulfonate monohydrate plus 270 mg oral paclitaxel and,
HM30181 methanesulfonate monohydrate plus 270 mg oral paclitaxel followed by IV paclitaxel.
Treatment details:
80 mg/m2 IV paclitaxel (as Taxol registered trademark or generic) infused over 1 hour (Day 1 or Day 8) plus premedicatio
Crossover Design: Study treatments will be administered on consecutive weeks with 1 week between each treatment administration. There are two sequences; IV paclitaxel followed by 15 mg oral HM30181 methanesulfonate monohydrate plus 270 mg oral paclitaxel and, HM30181 methanesulfonate monohydrate plus 270 mg oral paclitaxel followed by IV paclitaxel. Treatment details: 80 mg/m2 IV paclitaxel (as Taxol registered trademark or generic) infused over 1 hour (Day 1 or Day 8) plus premedication per standard local practice, or 15 mg oral HM30181 methanesulfonate monohydrate plus 270 mg oral paclitaxel (Days 1 and 2 or Days 8 and 9). HM30181AK-US tablet will be administered 1 hour before oral paclitaxel; no premedication is allowed during this treatment sequence. Qualified staff will administer IV paclitaxel treatment and monitor the subject for safety. Subjects will remain at the study site for at least the first 24 hours after dosing of IV paclitaxel for PK blood sample collection. Qualified staff will administer HM30181 methanesulfonate monohydrate plus 270 mg oral paclitaxel. Subjects will remain at the study site for the first 48 hours after dosing of Oraxol for PK blood sample collection. Subjects may leave the site and return for PK blood sample collections after 24 hours for IV paclitaxel or 48 hours of Oraxol PK blood collections have been completed and will return to the study site for the remaining PK blood collections. If more convenient, at the discretion of the investigator, the subjects may be discharged to a local motel or remain housed at the study site for the entirety of the PK blood collection periods for both IV paclitaxel and Oraxol. The second week of randomized treatment may be delayed for up to 2 weeks, if needed, to allow the subject to recover to less than or equal to Grade 1 CTCAE toxicity from the prior study treatment.
Sponsors
Kinex Pharmaceuticals, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent 2. 18 years of age and older 3. Cancer patients for which treatment with paclitaxel at 80 mg/m2 has been recommended by their oncologist, either as monotherapy or in combination with other agents. 4. Adequate bone marrow reserve as demonstrated by: Absolute neutrophil count (ANC) 1.0 109/L Platelet count 100 109/L Haemoglobin (Hgb) 9 g/L 5. Adequate liver function as demonstrated by: Total bilirubin of 20 micro mol/L or 30 micro mol/L for subjects with liver metastasis Alanine aminotransferase (ALT) 3 times upper limit of normal (ULN) or 5 times ULN if liver metastasis is present Alkaline phosphatase (ALP) 3 times ULN or 5 times ULN if bone metastasis is present 6. Adequate renal function as demonstrated by serum creatinine 177 micro mol/L or creatinine clearance greater than 50 mL/min as calculated by the Cockroft and Gault formula 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 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 prior to the first dose of study drug through the completion of protocol-specified PK sampling on Day 12 11. Willing to refrain from caffeine consumption for 12 hours prior to each dose of study drug through the completion of protocol-specified PK sampling for that dose on Day 5 or Day 12. Women must be postmenopausal (greater 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. 13. Sexually active male subjects 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
Eligible subjects must not have/be: 1. Currently taking a prohibited concomitant medication: Strong inhibitors or inducers of CYP3A4. Clinically significant inhibitors (gemfibrozil) or inducers (rifampin) of CYP2C8 Known P-gp inhibitors or inducers 2. 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 3. Received investigational agents within 14 days or 5 half-lives of the first study dosing day, whichever is longer. 4. Women of childbearing potential who are pregnant or breast feeding. 5. 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, clinically significant cardiac arrhythmia, chronic pulmonary disease requiring oxygen, known bleeding disorders, or psychiatric illness/social situations that would limit compliance with study requirements 6. Significant or uncontrolled cardiovascular disease or bleeding disorder 7. Major surgery to the upper gastrointestinal (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. Subjects whose allergy was due to the IV solvent (such as Cremophorregister trademark) and not paclitaxel will be eligible for this study.
Outcome results
None listed