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Trial registered on ANZCTR


Registration number
ACTRN12616000983404
Ethics application status
Approved
Date submitted
21/07/2016
Date registered
27/07/2016
Date last updated
29/01/2019
Date data sharing statement initially provided
29/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Oral Docetaxel for Prostate Cancer
Scientific title
An Open-label, Pilot Pharmacokinetic Study to Determine the Bioavailability, Safety, and Tolerability of a Single Dose of Oradoxel in Metastatic Prostate Cancer Patients Treated With Intravenous Docetaxel
Secondary ID [1] 289380 0
KX-ORADOX-002
Universal Trial Number (UTN)
U1111-1173-5473
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic prostate cancer 299018 0
Condition category
Condition code
Cancer 299076 299076 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In Treatment Period 1 the patients receive their last scheduled dose of IV docetaxel. In Treatment Period 2, 3 weeks after the IV docetaxel,.Oradoxel is to be administered. All participants will receive study treatments in the same order i.e. IV docetaxel followed by Oradoxel. Both study treatments will be administered by study staff in an oncology unit.
Participants will receive one dose of Oradoxel; Oradoxel comprises an HM30181AK-US tablet followed by oral docetaxel capsules. The oral docetaxel (at a dose of 75 mg/m2, 150 mg/m2, or 225 mg/m2, depending on the study cohort) is administered one hour after 15 mg HM30181AK-US tablet.
Premedication for Oradoxel can be given as clinically indicated, in the judgement of the investigator. The details of premedication given is entirely at the investigator's discretion, but should be in accordance with usual practice at the study site. Participants must abstain from alcohol consumption for 3 days before Study Period 1 until the Final Visit. Participants must refrain from caffeine consumption for 12 hours prior to dosing with Oradoxel and must fast at least 8 hours prior to and 4 hours after dosing with Oradoxel.
Intervention code [1] 294967 0
Treatment: Drugs
Comparator / control treatment
All participants receive both the study treatments and in the same order. IV docetaxel is the comparator treatment to Oradoxel as this is a pharmacokinetic and safety study. IV docetaxel is administered as per standard care for metastatic prostate cancer (e.g. dose and number of doses administered). The study starts just before the last scheduled dose of IV docetaxel is administered; this is followed by one dose of Oradoxel 3 weeks later. Therefore the Oradoxel dose is in addition to and following after the usual standard of care with IV docetaxel.
Control group
Active

Outcomes
Primary outcome [1] 298549 0
The primary endpoint is area under the concentration–time curve time 0 extrapolated to infinity (AUC0-inf) derived for each participant by noncompartmental analysis using plasma concentration-time data for oral and IV docetaxel.
Timepoint [1] 298549 0
After receiving IV docetaxel PK blood samples will be obtained at the following times:
Predose, at 2, 5, 8, 12, 20, 40, and 60 minutes during the infusion, and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 18, 24, 32, 48, 56, and 72 hours post-infusion.
After receiving Oradoxel PK blood samples will be obtained at the following times:
Predose, at 15, 30 and 45 minutes and 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 32, 48, 56, 72 and 96 hours after you finish taking the oral docetaxel capsules.
Secondary outcome [1] 324546 0
Maximum observed concentration (Cmax) after administration of oral and IV docetaxel
Timepoint [1] 324546 0
After receiving IV docetaxel PK blood samples will be obtained at the following times:
Predose, at 2, 5, 8, 12, 20, 40, and 60 minutes during the infusion, and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 18, 24, 32, 48, 56, and 72 hours post-infusion.
After receiving Oradoxel PK blood samples will be obtained at the following times:
Predose, at 15, 30 and 45 minutes and 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 32, 48, 56, 72 and 96 hours after taking the oral docetaxel capsules.
Secondary outcome [2] 324547 0
Area under the concentration–time curve time 0 to time of last quantifiable concentration(AUC0-t)
Timepoint [2] 324547 0
After receiving IV docetaxel PK blood samples will be obtained at the following times:
Predose, at 2, 5, 8, 12, 20, 40, and 60 minutes during the infusion, and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 18, 24, 32, 48, 56, and 72 hours post-infusion.
After receiving Oradoxel PK blood samples will be obtained at the following times:
Predose, at 15, 30 and 45 minutes and 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 32, 48, 56, 72 and 96 hours after taking the oral docetaxel capsules.
Secondary outcome [3] 324548 0
Time at which the highest drug concentration occurs (Tmax)
Timepoint [3] 324548 0
After receiving IV docetaxel PK blood samples will be obtained at the following times:
Predose, at 2, 5, 8, 12, 20, 40, and 60 minutes during the infusion, and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 18, 24, 32, 48, 56, and 72 hours post-infusion.
After receiving Oradoxel PK blood samples will be obtained at the following times:
Predose, at 15, 30 and 45 minutes and 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 32, 48, 56, 72 and 96 hours after taking the oral docetaxel capsules.
Secondary outcome [4] 324549 0
Terminal elimination phase half-life (t1/2)
Timepoint [4] 324549 0
After receiving IV docetaxel PK blood samples will be obtained at the following times:
Predose, at 2, 5, 8, 12, 20, 40, and 60 minutes during the infusion, and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 18, 24, 32, 48, 56, and 72 hours post-infusion.
After receiving Oradoxel PK blood samples will be obtained at the following times:
Predose, at 15, 30 and 45 minutes and 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 32, 48, 56, 72 and 96 hours after you finish taking the oral docetaxel capsules.
Secondary outcome [5] 324550 0
The safety and tolerability of Oradoxel compared with IV docetaxel will be
assessed by evaluation of laboratory findings.
Safety laboratory tests will include haematology, biochemistry (i.e. electrolytes, liver and renal function tests) and other routine tests (e.g. glucose, triglycerides, cholesterol, protein) and urinalysis.
Timepoint [5] 324550 0
Blood should be collected within 4 days prior to dosing on Day 1 of each study period (preferably prior to starting premedication for each study period), and at weekly intervals (Day 7 and 14 of each study period), and at the Final Visit. The baseline collection for Study Period 2 will also serve as the Day 21 measurement for Study Period 1.
Secondary outcome [6] 324555 0
The safety and tolerability of Oradoxel compared with IV docetaxel will be assessed by evaluation of Adverse Events. This is the first clinical trial with Oradoxel but the possible adverse effects are expected to be similar to those with IV docetaxel. These can be serious (e.g. allergic reactions, liver toxicity, fluid retention, bone marrow depression); other side effects include changes in sense of taste, shortness of breath , constipation, decreased appetite, changes in fingernails or toenails, swelling of hands, face or feet, fatigue, joint and muscle pain, nausea and vomiting, diarrhoea, mouth or lips sores, hair loss, rash and other skin reactions, redness of the eye and excess tearing.
The most commonly reported side effects of the HM30181AK-US tablet are: constipation, dyspepsia, abdominal pain, somnolence, fatigue, chest discomfort, dizziness, nasal congestion, throat irritation, runny nose, and a hoarse, rough or scratchy voice.
Adverse reactions will be assessed by asking the participant, physical examinations, and by observations by site staff.
Timepoint [6] 324555 0
From Screening until the Final Visit, which is scheduled for Day 21 of Treatment Period 2. Participants will be assessed at regular intervals while at the study site to Day 2 and at each study visit on Days 3, 4, 7 and 14 after IV docetaxel and on Days 3, 4, 5, 7, 14 and 21 after Oradoxel.
Secondary outcome [7] 324556 0
The safety and tolerability of Oradoxel compared with IV docetaxel will be assessed by evaluation of concomitant medications.
All concomitant medications will be recorded on source documents and then entered into the eCRF.
Timepoint [7] 324556 0
From Screening until the Final Visit, which is scheduled for Day 21 of Treatment Period 2.
Secondary outcome [8] 324557 0
The safety and tolerability of Oradoxel compared with IV docetaxel will be assessed by evaluation of vital signs.
Vital signs (pulse rate, systolic/diastolic blood pressure, respiration and
temperature) will be measured at each study visit.
Timepoint [8] 324557 0
Vital sign measurements should be taken at Screening, Baseline (Day-1), and predose on
Day 1 for both study periods, in the morning of all inpatient days, and when the participant
first arrives for PK sampling on outpatient days. Vital signs should also be taken at the Final
Visit.
Secondary outcome [9] 324558 0
The safety and tolerability of Oradoxel compared with IV docetaxel will be assessed by evaluation of physical examinations.
Physical examinations will include an assessment of general appearance; head, eyes, ears, nose, and throat; thorax (including cardiovascular and respiratory systems); abdomen; skin; musculoskeletal; extremities and neurological examination. Additional examinations will be performed as
clinically indicated to assess AEs.
Timepoint [9] 324558 0
Complete physical examinations will be performed at Screening, and the Final Visit. All other physical examinations do not require complete examinations but will be targeted to the signs and symptoms related to adverse event reporting, and conducted on Day -1 of each study period.
.
Secondary outcome [10] 324559 0
The safety and tolerability of Oradoxel compared with IV docetaxel will be assessed by evaluation of ECGs.
Timepoint [10] 324559 0
At Screening, Day 1 for both study periods - 2 hours post dosing of Oradoxel and IV docetaxel and at the final visit.
Secondary outcome [11] 324560 0
The safety and tolerability of Oradoxel compared with IV docetaxel will be assessed by evaluation of ECOG performance status.
Timepoint [11] 324560 0
At Screening, baseline for study period 2 and at the final visit.

Eligibility
Key inclusion criteria
Eligible participants must be males at least 18 years of age with metastatic prostate cancer who are scheduled to receive their final prescribed dose of treatment with IV docetaxel. Patients may be receiving steroid treatment or ADT for prostate cancer, but other concomitant cancer chemotherapy is not permitted.
They must have:
- adequate hematologic status as demonstrated by not requiring transfusion support or granulocyte-colony stimulating factor (G-CSF);
- Adequate liver function as demonstrated by: Total bilirubin of less than the upper limit of normal (ULN); Aspartate transaminase (AST) and alanine aminotransferase (ALT) less than/equal to 1.5 times ULN; Alkaline phosphatase (ALP) less than/equal to 2.5 times ULN or less than 5 times ULN if bone metastases are present
- Adequate renal function as demonstrated by serum creatinine less than/equal to 177 micromole/L or creatinine clearance greater than 60 mL/min as calculated by the Cockcroft and Gault formula
Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy of at least 6 months; Willing to fast for 8 hours before and 4 hours after Oradoxel administration; Willing to abstain from alcohol consumption from 3 days prior Study Period 1 through to the Final Visit; Willing to refrain from caffeine consumption for 12 hours prior to each dose of study drug through the completion of protocol-specified PK sampling time-points; Sexually active participants must use a barrier method of contraception during the study and agree to continue the use of contraception for at least 30 days after the last dose of study drug.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Eligible participants must not be
- currently taking a prohibited concomitant medication;
- have unresolved toxicity from prior chemotherapy (participants must have recovered from all significant toxicity to less than or equal to Grade 1 CTCAE toxicity from previous anticancer treatments or previous investigational agents);
- planning to receive other medical, surgical, or radiological treatments for prostate cancer during the course of this study;
- received investigational agents within 14 days or 5 half-lives prior to the first study dosing day, whichever is longer;
- uncontrolled intercurrent illness; no 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;
- known history of allergy to docetaxel, Cremophor (Registered Trademark), or polysorbate 80 (Tween 80);
- any other condition which the Investigator believes would make participation in the study not acceptable.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All participants will receive both study treatments and in the same order (i.e. IV docetaxel followed by oral Oradoxel).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Bio-availability
Statistical methods / analysis
The PK parameters will be derived for each participant by noncompartmental analysis using plasma concentration-time data for oral and IV docetaxel.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 7940 0
New Zealand
State/province [1] 7940 0
Otago

Funding & Sponsors
Funding source category [1] 293761 0
Commercial sector/Industry
Name [1] 293761 0
Kinex Pharmaceuticals Inc
Address [1] 293761 0
20 Commerce Drive
Cranford
New Jersey 07016
Country [1] 293761 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Kinex Pharmaceuticals Inc
Address
20 Commerce Drive
Cranford
New Jersey 07016
Country
United States of America
Secondary sponsor category [1] 292591 0
Commercial sector/Industry
Name [1] 292591 0
Zenith Technology Corporation Ltd.
Address [1] 292591 0
156 Frederick Street
Dunedin 9016
Country [1] 292591 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295198 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 295198 0
C/- Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 295198 0
New Zealand
Date submitted for ethics approval [1] 295198 0
01/10/2015
Approval date [1] 295198 0
02/11/2015
Ethics approval number [1] 295198 0
15/STH/182

Summary
Brief summary
Oradoxel is a combination of an oral tablet, HM30181 methanesulfonate, and
capsules that contain docetaxel. HM30181 is a drug that helps the body
absorb docetaxel, a drug used to treat cancer. The purpose of this study is
to measure the levels of docetaxel in your blood at different times when
given by intravenous (IV) drip (through a vein in your arm) compared with
the levels of docetaxel at different times in your blood when given by
mouth (as Oradoxel).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66474 0
Dr Christopher Jackson
Address 66474 0
Department of Oncology Dunedin Hospital Southern District Health Board
201 Great King Street Dunedin 9016
Country 66474 0
New Zealand
Phone 66474 0
+64 3 474 0999 ext 9698
Fax 66474 0
Email 66474 0
Christopher.jackson@southerndhb.govt.nz
Contact person for public queries
Name 66475 0
Mrs Linda Folland
Address 66475 0
Zenith Technology Corporation, Ltd. 156 Frederick Street Dunedin 9016
Country 66475 0
New Zealand
Phone 66475 0
+643 477 9669
Fax 66475 0
Email 66475 0
Linda.Folland@Zenithtechnology.co.nz
Contact person for scientific queries
Name 66476 0
Dr E. Douglas Kramer
Address 66476 0
Kinex Pharmaceuticals, Inc. 20 Commerce Drive Cranford New Jersey
07016
Country 66476 0
United States of America
Phone 66476 0
+1 908-272-0628
Fax 66476 0
Email 66476 0
dkramer@kinexpharma.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Undecided.
What supporting documents are/will be available?
No other documents available
Summary results
No Results