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A DRF Study to Evaluate Safety, Tolerability, PK, and Activity of Oradoxel Monotherapy in Subjects w Adv. Malignancies

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02963168
Recruitment Status : Unknown
Verified January 2019 by Athenex, Inc..
Recruitment status was:  Recruiting
First Posted : November 15, 2016
Last Update Posted : October 17, 2019
Sponsor:
Information provided by (Responsible Party):
Athenex, Inc.

Tracking Information
First Submitted Date  ICMJE October 7, 2016
First Posted Date  ICMJE November 15, 2016
Last Update Posted Date October 17, 2019
Actual Study Start Date  ICMJE April 20, 2017
Estimated Primary Completion Date March 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 9, 2016)
The maximum tolerated dose (MTD) of Oradoxel based on dose-limiting toxicity (DLT) in subjects with advanced malignancies [ Time Frame: 3 weeks ]
The MTD will be the highest dose at which no more than 1 of 6 subjects experience a DLT during treatment and Oradoxel pharmacokinetics are acceptable.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2016)
  • Safety assessment using AEs of Oradoxel [ Time Frame: Weekly, up to 24 months ]
  • Safety assessment using SAEs of Oradoxel [ Time Frame: Weekly, up to 24 months ]
  • Laboratory evaluation for hematology [ Time Frame: Weekly, up to 24 months ]
  • Blood chemistry [ Time Frame: Weekly, up to 24 months ]
  • Urine analysis [ Time Frame: Weekly, up to 24 months ]
  • Periodic measurements of ECGs [ Time Frame: Screening, Day 1, every 6 weeks thereafter up to 24 months ]
  • Periodic measurements of vital signs [ Time Frame: Weekly, up to 24 months ]
  • The incidence of unacceptable toxicity with Oradoxel [ Time Frame: 24 months ]
    Unacceptable toxicity graded according to CTCAE v4.03
  • The recommended Phase 2 dose (RP2D) of Oradoxel [ Time Frame: 24 months ]
    Upon determination of the overall MTD for Oradoxel, the safety and PK profile of the study treatment from all Treatment Periods will be reviewed to determine the recommended Phase 2 dose.
  • The amount of docetaxel and HM30181A in blood stream by Area under the plasma concentration versus time curve (AUC) [ Time Frame: Part 1: 16 timepoints over 504 hours; Part 2: 26 timepoints over 480 hours ]
  • The peak plasma concentration (Cmax) and Minimum plasma concentration (Cmin) [ Time Frame: Part 1: 16 timepoints over 504 hours; Part 2: 26 timepoints over 480 hours ]
  • A biological half-life or elimination half-life (t1/2) [ Time Frame: Part 1: 16 timepoints over 504 hours; Part 2: 26 timepoints over 480 hours ]
  • The accumulation ratio (R) [ Time Frame: Part 1: 16 timepoints over 504 hours; Part 2: 26 timepoints over 480 hours ]
  • The apparent total clearance of the drug from plasma (CL/F) [ Time Frame: Part 1: 16 timepoints over 504 hours; Part 2: 26 timepoints over 480 hours ]
  • The apparent volume of distribution (Vd/F) [ Time Frame: Part 1: 16 timepoints over 504 hours; Part 2: 26 timepoints over 480 hours ]
  • To evaluate tumor response [ Time Frame: Every 12 weeks, up to 24 months ]
    Tumor response will be evaluated according to RECIST v1.1
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 DRF Study to Evaluate Safety, Tolerability, PK, and Activity of Oradoxel Monotherapy in Subjects w Adv. Malignancies
Official Title  ICMJE A Dose Regimen-Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of Oradoxel Monotherapy in Subjects With Advanced Malignancies
Brief Summary This is a nonrandomized, open-label, dose escalation, safety, activity, and PK study to determine the MTD and optimal dosing regimen of Oradoxel. No control group has been included.
Detailed Description

This is a multicenter, open-label, safety, tolerability, pharmacokinetic, and activity study. Eligible subjects will be adults with advanced solid malignancies.

Groups of 3 to 6 subjects will receive a single dose of Oradoxel and will be followed for toxicity. If non linearity in PK is observed, additional subjects will receive Oradoxel as 2 single daily doses once every three weeks. Subjects who tolerate the drug and have stable disease or better response will be eligible to receive ongoing treatment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE Drug: Oradoxel
oral docetaxel will be supplied in capsules and oral HM30181A-UK tablets
Other Name: oral docetaxel + oral HM30181A
Study Arms  ICMJE Experimental: Oradoxel
To determine the MTD of Oradoxel (oral docetaxel and oral HM30181A) when administered once every 3 weeks, then to determine the MTD of Oradoxel (oral docetaxel and oral HM30181A) when administered for two days every three weeks.
Intervention: Drug: Oradoxel
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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 9, 2016)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2020
Estimated Primary Completion Date March 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed written informed consent
  2. ≥18 years of age
  3. Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  4. Docetaxel monotherapy is a reasonable treatment in the judgement of the Investigator
  5. Measurable disease as per RECIST v1.1 criteria
  6. Able to swallow oral medication as an intact dosage form
  7. Adequate hematologic status as demonstrated by not requiring transfusion support or granulocyte-colony stimulating factor (G-CSF) to maintain: Absolute neutrophil count (ANC) ≥1500 cells/mm3, Platelet count ≥100 x 109/L, Hemoglobin (Hgb) ≥10 g/dL
  8. Adequate liver function as demonstrated by: Total bilirubin of < upper limit of normal (ULN), Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤1.5 × ULN, Alkaline phosphatase (ALP) ≤2.5x ULN or <5x ULN if bone metastases are present, Normal serum albumin
  9. Adequate renal function as demonstrated by serum creatinine ≤1.5 x ULN or creatinine clearance>60 mL/min as calculated by the Cockroft and Gault formula
  10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  11. Life expectancy of at least 3 months
  12. Willing to fast for 6 hours before and 2 hours after Oradoxel administration
  13. Females must be postmenopausal (>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 30 days after their last dose of study drug.
  14. 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:

  1. Currently taking a prohibited concomitant medication, other than a premedication, that are/is:

    • Strong inhibitors (eg, ketoconazole) or inducers (eg, rifampicin or St. John's Wort) of CYP3A4 (within 2 weeks prior to the start of dosing in the study)
    • Strong P-gp inhibitors or inducers. Subjects 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 PK sampling after the administration of the second study treatment
    • An oral medication with a narrow therapeutic index known to be a P-gp substrate within 24 hours prior to start of dosing in the study
  2. Unresolved toxicity from prior chemotherapy (subjects must be recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous investigational products.
  3. Planning to receive other medical, surgical, or radiological cancer treatments during the course of this study
  4. Received investigational agents within 14 days or 5 half-lives prior to the first study dosing day, whichever is longer
  5. Require therapeutic use of anticoagulants
  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 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 docetaxel, Cremophor or polysorbate 80 (Tween 80)
  9. Evidence of fluid retention at Screening (including, for example, peripheral edema, pleural effusion, or ascites on physical or radiological examination) or history of severe capillary leak syndrome
  10. Any other condition which the Investigator believes would make 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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02963168
Other Study ID Numbers  ICMJE KX-ORADOX-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Athenex, Inc.
Original Responsible Party Kinex Pharmaceuticals Inc.
Current Study Sponsor  ICMJE Athenex, Inc.
Original Study Sponsor  ICMJE Kinex Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: David Cutler, MD Athenex, Inc.
PRS Account Athenex, Inc.
Verification Date January 2019

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