Clinical trial NCT03892018: The Effect of Food on the Pharmacokinetics of Paclitaxel Administered Orally as Oraxol
Official title: An Open-label, Crossover Study of the Effect of Food on the Pharmacokinetics of Paclitaxel Administered Orally as Oraxol
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor, Adult
Lead sponsor: Athenex, Inc.
Sponsor class: INDUSTRY
First posted: 2019-03-27
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This will be an open-label, 2-part, crossover study to assess the effect of food on Oraxol exposure. The study will consist of the following periods: Screening, Baseline, Periods 1 and 2 (Part A), Treatment (Part B), and Follow-up. Part A will assess the effect of food on Oraxol pharmacokinetics. In Part A, subjects will be randomized to the sequence (fed/fasted or fasted/fed conditions) under which they will be administered single-dose treatment after an overnight fast. There will be a minimum of 7 days after Period 1 treatment before subjects cross over to Period 2 treatment. Subjects who have participated in the PK assessments in Part A of the study may continue into Part B, during which Oraxol will be dosed for 3 consecutive days per week under fasting conditions.
Primary purpose: TREATMENT

Brief summary: This is multicenter, open-label, 2-part crossover study. Eligible subjects will have metastatic or unresectable solid tumors. This study includes a pretreatment and treatment phase. The pretreatment phase consists of screening and baseline. The treatment phase consists of Periods 1 and 2 (Part A), Treatment (Part B), and Follow-up.


Eligibility criteria: Inclusion Criteria:

* Signed written informed consent
* 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.
* Measurable disease as per RECIST v1.1 criteria
* Adequate hematologic status
* Adequate liver function.
* Adequate renal function
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* Life expectancy of at least 3 months.
* Women must be postmenopausal or surgically sterile.
* Sexually active male subjects must use a barrier method of contraception during the study.
* Able to consume the prescribed meals

Exclusion Criteria:

* Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous investigational products (IPs).
* Received IPs within 21 days or 5 half-lives of the first dosing day, whichever is shorter
* Are currently receiving other medications or radiation intended for the treatment of their malignancy. Hormonal therapy is allowed.
* Women of childbearing potential who are pregnant or breastfeeding.
* Currently taking a concomitant medication, other than a premedication, that is:

  * A strong P-glycoprotein (P-gp) inhibitor or inducer.
  * An oral medication with a narrow therapeutic index known to be a P-gp substrate.
  * Medications known to be strong inhibitors or inducers of cytochrome P450 (CYP) 2C8 or medications known to be strong CYP3A4 inhibitors or inducers.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or any concomitant illness that would limit compliance with study requirements.
* Major surgery to the upper gastrointestinal (GI) tract, or have a history of GI disease that may interfere with oral drug absorption.
* Cirrhosis of the liver or known active hepatitis B, hepatitis C, or HIV
* History of hypersensitivity to paclitaxel, not attributed to a hypersensitivity-type reaction to Cremophor

Primary outcomes:
measure: Comparison of the concentration-time profile of Oral Paclitaxel in plasma for 168 hours when taken with or without food.
timeFrame: 24 months
Secondary outcomes:
measure: Comparison of the concentration-time profile of HM30181 in plasma for 168 hours when taken with or without food.
timeFrame: 24 months
measure: The proportion of patients with tumor responses after the initiation of treatment.
timeFrame: At baseline and every 8 weeks through study completion, approximately 24 months
measure: Incidence of Adverse Events (Safety and Tolerability)
timeFrame: 24 months
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Care Centre
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Northern Institute for Cancer Care
Study officials:
affiliation: Athenex, Inc.
name: David Cutler, MD
role: STUDY_DIRECTOR
References: