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A Safety Study of Oraxol (HM30181 + Oral Paclitaxel) in Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04180384
Recruitment Status : Recruiting
First Posted : November 27, 2019
Last Update Posted : November 27, 2019
Sponsor:
Information provided by (Responsible Party):
Athenex, Inc.

Tracking Information
First Submitted Date  ICMJE June 13, 2019
First Posted Date  ICMJE November 27, 2019
Last Update Posted Date November 27, 2019
Actual Study Start Date  ICMJE September 23, 2015
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2019)
Safety and tolerability of Oraxol (Incidence of Treatment-Emergent Adverse Events) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2019)
  • Sustained oral bioavailability of paclitaxel following multiple dosing [ Time Frame: 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. ]
    Oraxol PK data from this study will be compared with Oraxol PK data from study KX-ORAX-002.
  • the relative bioavailability of paclitaxel tablets vs paclitaxel capsules (Group B only) [ Time Frame: 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. ]
    For Group B, 8 subjects will be enrolled and the geometric mean ratio (GMR) will be calculated comparing the Cmax and AUC0-∞ of the tablet and capsule formulations of paclitaxel following oral administration.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety Study of Oraxol (HM30181 + Oral Paclitaxel) in Cancer Patients
Official Title  ICMJE A Safety Study of Oraxol (HM30181 + Oral Paclitaxel) in Cancer Patients
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 that the blood levels of paclitaxel after several doses of Oraxol are similar to the levels expected.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE Drug: Oraxol
Other Names:
  • HM30181 methanesulfonate monohydrate
  • Oral paclitaxel capsules
  • Oral paclitaxel tablets
Study Arms  ICMJE Experimental: Oraxol (paclitaxel + HM30181AK-US)

Oraxol paclitaxel - supplied as 30-mg capsules or tablets

Oraxol HM30181 methansulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets

Intervention: Drug: Oraxol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 26, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 109/L
    • Platelet count ≥100 x 109/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.

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jackson Christopher, MD +64 3 474 0999 ext 9698 Christopher.jackson@southerndhb.govt.nz
Listed Location Countries  ICMJE Australia,   New Zealand,   Taiwan,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04180384
Other Study ID Numbers  ICMJE KX-ORAX-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Athenex, Inc.
Study Sponsor  ICMJE Athenex, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jackson Christopher, MD Dunedin Hospital
PRS Account Athenex, Inc.
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP