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

• Sponsor: Athenex, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03892018
• Collaborator: (none)
• Enrollment: 36
• Locations: 3
• Arms: 2
• Anticipated Duration (Months): 38.9
• Patients Per Site: 12
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor, Adult	Drug: Oraxol	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• 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.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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Crossover Study of the Effect of Food on the Pharmacokinetics of Paclitaxel Administered Orally as Oraxol
• Actual Study Start Date: Aug 5, 2019
• Anticipated Primary Completion Date: Jul 15, 2022
• Anticipated Study Completion Date: Oct 31, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. Comparison of the concentration-time profile of HM30181 in plasma for 168 hours when taken with or without food. [24 months]

2. The proportion of patients with tumor responses after the initiation of treatment. [At baseline and every 8 weeks through study completion, approximately 24 months]

   RECIST v1.1 criteria defined as complete response, partial response, stable disease or progressive disease

3. Incidence of Adverse Events (Safety and Tolerability) [24 months]

   Evaluate the safety of Oraxol. Number of participants with treatment-related adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Beatson West of Scotland Cancer Care Centre	Glasgow		United Kingdom	G12 0YN
2	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
3	The Northern Institute for Cancer Care	Newcastle Upon Tyne		United Kingdom	NE2 4HH

Sponsors and Collaborators

• Athenex, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Athenex, Inc.
• ClinicalTrials.gov Identifier: NCT03892018
• Other Study ID Numbers: KX-ORAX-012
• First Posted: Mar 27, 2019
• Last Update Posted: Feb 17, 2022
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Paclitaxel

Study Results

No Results Posted as of Feb 17, 2022