The Effect of Food on the Pharmacokinetics of Paclitaxel Administered Orally as Oraxol

An Open-label, Crossover Study of the Effect of Food on the Pharmacokinetics of Paclitaxel Administered Orally as Oraxol

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: Oraxol

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • The Beatson West of Scotland Cancer Care Centre
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Newcastle Upon Tyne, United Kingdom, NE2 4HH
    • The Northern Institute for Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fed/ Fasted Treatment Sequence; Subjects will be assigned a fed/fasted sequence. Fed sequence- subjects will fast overnight and continue fasting until they consume a standardized test meal at a predetermined time after paclitaxel administration. Fasted Sequence- subjects will fast overnight and continue fasting until 4 hours post paclitaxel dose.	Drug: Oraxol; Oraxol will be supplied as paclitaxel capsules and HM30181AK-US tablets.; Other Names: Paclitaxel and HM30181AK-US
Active Comparator: Fasted/ Fed Treatment Sequence; Subjects will be assigned a fasted/fed sequence. Fasted Sequence- subjects will fast overnight and continue fasting until 4 hours post paclitaxel dose. Fed sequence- subjects will fast overnight and continue fasting until they consume a standardized test meal at a predetermined time after paclitaxel administration.	Drug: Oraxol; Oraxol will be supplied as paclitaxel capsules and HM30181AK-US tablets.; Other Names: Paclitaxel and HM30181AK-US

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of the concentration-time profile of Oral Paclitaxel in plasma for 168 hours when taken with or without food.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the concentration-time profile of HM30181 in plasma for 168 hours when taken with or without food.		24 months
The proportion of patients with tumor responses after the initiation of treatment.	RECIST v1.1 criteria defined as complete response, partial response, stable disease or progressive disease	At baseline and every 8 weeks through study completion, approximately 24 months
Incidence of Adverse Events (Safety and Tolerability)	Evaluate the safety of Oraxol. Number of participants with treatment-related adverse events.	24 months

Collaborators and Investigators

• Sponsor: Athenex, Inc.
• Investigators: Study Director: David Cutler, MD, Athenex, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2019
• Primary Completion (Actual): May 12, 2023
• Study Completion (Actual): May 12, 2023

Study Registration Dates

• First Submitted: March 19, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Actual): May 22, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: KX-ORAX-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No