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

NCT03892018 | Terminated Phase 1 FDA Drug

• 1 other identifier: KX-ORAX-012
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

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.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (1)

• Comparison of the concentration-time profile of Oral Paclitaxel in plasma for 168 hours when taken with or without food.

  24 months

Secondary Outcomes (3)

• 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.

  At baseline and every 8 weeks through study completion, approximately 24 months

• Incidence of Adverse Events (Safety and Tolerability)

  24 months

Study Arms (2)

Fed/ Fasted Treatment Sequence

ACTIVE COMPARATOR

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

Fasted/ Fed Treatment Sequence

ACTIVE COMPARATOR

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

Interventions

Oraxol DRUG

Oraxol will be supplied as paclitaxel capsules and HM30181AK-US tablets.

Also known as: Paclitaxel and HM30181AK-US

Fasted/ Fed Treatment Sequence; Fed/ Fasted Treatment Sequence

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Athenex, Inc.: lead

Study Sites (3)

The Beatson West of Scotland Cancer Care Centre

Glasgow, G12 0YN, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

The Northern Institute for Cancer Care

Newcastle upon Tyne, NE2 4HH, United Kingdom

Location

MeSH Terms

Interventions

Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• David Cutler, MD

  Athenex, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: March 27, 2019
• Study Start: August 5, 2019
• Primary Completion: May 12, 2023
• Study Completion: May 12, 2023
• Last Updated: May 22, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)