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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.

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.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: Oraxol Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Safety Study of Oraxol (HM30181 + Oral Paclitaxel) in Cancer Patients
Actual Study Start Date : September 23, 2015
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
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

Drug: Oraxol
Other Names:
  • HM30181 methanesulfonate monohydrate
  • Oral paclitaxel capsules
  • Oral paclitaxel tablets




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04180384


Contacts
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Contact: Jackson Christopher, MD +64 3 474 0999 ext 9698 Christopher.jackson@southerndhb.govt.nz

Locations
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Australia
Monash Medical Centre Recruiting
Clayton, Australia, 3168
Contact: Eva Segelov, MD    +61 3 8572 2788    Eva.Segelov@monash.edu   
Principal Investigator: Eva Segelov, MD         
New Zealand
Auckland City Hospital Recruiting
Auckland, New Zealand
Contact: Sanjeev Deva, MD    +64 9 367 0000    sanjeevd@adhb.govt.nz   
Principal Investigator: Sanjeev Deva, MD         
Christchurch Hospital Not yet recruiting
Christchurch, New Zealand
Contact: Matthew Strother, MD    +643 3640 640    matthew.strother@cdhb.health.nz   
Principal Investigator: Matthew Strother, MD         
Dunedin Hospital Recruiting
Dunedin, New Zealand
Contact: Christopher Jackson, MD    +64 3 474 0999 ext 9698    Christopher.jackson@southerndhb.govt.nz   
Principal Investigator: Christopher Jackson, MD         
Wellington Regional Hospital Recruiting
Wellington, New Zealand
Contact: Kate Clarke    +644 385 5999    Kate.clarke@ccdhb.org.nz   
Principal Investigator: Kate Clarke, MD         
Taiwan
Taipei Medical University Shuang Ho Hospital Recruiting
New Taipei City, Taiwan, 23561
Contact: Tsu-Yi Chao, MD, DMS, PhD    886227361661 ext 3229    10575@s.tmu.edu.tw   
Principal Investigator: Tsu-Yi Chao, MD, DMS, PhD         
Tri-Service General Hospital Recruiting
Taipei, Taiwan, 114
Contact: Ming-Shen Dai, MD    +886-2-8792-3311 ext 12623    dms1201@gmail.com   
Principal Investigator: Ming-Shen Dai, MD         
Lotung Poh-Ai Hospital Recruiting
Yilan, Taiwan
Contact: Hsien-Tang Yen, MD         
Principal Investigator: Hsien-Tang Yen, MD         
United Kingdom
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom, M20 4BX
Contact: Louise Carter, MD    +44 (0) 161 918 2388    Louise.Carter@christie.nhs.uk   
Principal Investigator: Louise Carter, MD         
Sponsors and Collaborators
Athenex, Inc.
Investigators
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Principal Investigator: Jackson Christopher, MD Dunedin Hospital

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Responsible Party: Athenex, Inc.
ClinicalTrials.gov Identifier: NCT04180384    
Other Study ID Numbers: KX-ORAX-003
First Posted: November 27, 2019    Key Record Dates
Last Update Posted: November 27, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action