A Safety Study of Oraxol (HM30181 + oral paclitaxel) in Cancer Patients
Kinex Pharmaceuticals Inc
44 participants
Sep 16, 2015
Interventional
Conditions
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. Once the dose of Oraxol has been confirmed in the KX-ORAX-002 study, then enrolment of patients who have not participated in the KX-ORAX-002 study will be allowed. 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 that the blood levels of paclitaxel after several doses of Oraxol are similar to the levels expected. Participants in Group B (N=8) will receive the same weekly paclitaxel capsule treatment as the remainder of the subjects except for 1 dosing week (at least 1 week following the paclitaxel capsule PK sampling period) during which they will receive paclitaxel tablets and undergo PK assessments.
Eligibility
Inclusion Criteria14
- 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 Criteria8
- 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.
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Interventions
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 progression of disease, withdrawal of consent, termination of the study by the Sponsor, or other specified reason. If needed at any time, treatment may be delayed for up to 2 weeks to allow a participant to recover to less than or equal to Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) toxicity from prior chemotherapy.
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ACTRN12615000881538