A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Activity of Oraxol in Subjects With Advanced Malignancies

A Dose-regimen Finding Study to Evaluate Safety, Tolerability, Pharmacokinetics and Activity of Oraxol in Subjects With Advanced Malignancies

This is a standard "3+3" Phase 1b study to determine the MTD of Oraxol (paclitaxel + HM30181 Methanesulfonate monohydrate) in subjects with advanced malignancies that may be metastatic or unresectable with measurable malignant lesion(s) per RECIST Version 1.1 criteria.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Oraxol

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 800045
      • University of Colorado Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed written informed consent
2. ≥ 18 years of age
3. 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.
4. Measurable disease as per RECIST Version 1.1 criteria.

5. Adequate bone marrow reserve as demonstrated by

   • Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L
   • Platelet count ≥ 100 x 10⁹/L
   • Hemoglobin (Hgb) ≥ 9 g/L

6. Adequate liver function as demonstrated by

   • Total bilirubin of ≤ 1.5 mg/dL or ≤ 2.0 mg/dL for subjects with liver metastasis
   • Alanine aminotransferase (ALT)≤ 3 x upper limit of normal (ULN) or ≤ 5x ULN if liver metastasis is present
   • ALP ≤ 3 x ULN or ≤ 5 x ULN if bone metastasis is present
7. Adequate renal function as demonstrated by serum creatinine ≤ 1.5 x ULN, or 24-hr urine creatinine clearance calculation >60 mL/min
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
9. Life expectancy of at least 3 months
10. Subjects who are not currently taking prohibited medication
11. Women must be postmenopausal (> 12 months without menses) or surgically sterile (ie, by hysterectomy and/or bilateral oophorectomy) or must be using effective contraception

Exclusion Criteria:

1. Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous investigational agents
2. Received investigational agents within 14 days or 5 half-lives of the first study dosing day, whichever is longer.
3. Women of childbearing potential who are pregnant or breast feeding.
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia, chronic pulmonary disease requiring oxygen, known bleeding disorders, or psychiatric illness/social situations that would limit compliance with study requirements
5. Significant or uncontrolled cardiovascular disease or bleeding disorder
6. 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
7. Subjects with a known history of allergy to paclitaxel. Subjects whose allergy was due to the IV solvent (such as Cremophor®) and not paclitaxel will be eligible for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oraxol Arm 1; HM30181AK-US tablet administered as a single oral dose of xmg on Days x, y, and z of each cycle Paclitaxel administered as a fixed oral daily dose of xmg (nine xmg capsules) starting on Days x, y, and z of each cycle. Depending on the cohort, subjects will receive 2, 3, 4, or 5 consecutive days of paclitaxel per week.	Drug: Oraxol; Oraxol (Paclitaxel + HM30181AK). Paclitaxel will be supplied as 30 mg capsules and HM30181AK-US will be supplied as 15 mg tablets.
Experimental: Oraxol Arm 2; HM30181AK-US tablet administered as a single oral dose of xmg daily with each dose of Paclitaxel Paclitaxel administered as a fixed oral daily dose of xmg (nine xmg capsules) starting on Days x, y, and z of each cycle. Depending on the cohort, subjects will receive 2, 3, 4, or 5 consecutive days of paclitaxel per week.	Drug: Oraxol; Oraxol (Paclitaxel + HM30181AK). Paclitaxel will be supplied as 30 mg capsules and HM30181AK-US will be supplied as 15 mg tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the maximum tolerated dose (MTD) of Oraxol in subjects with advanced malignancies	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the recommended Phase 2 dose (RP2D) of Oraxol	one year six months

Collaborators and Investigators

• Sponsor: Kinex Pharmaceuticals Inc.
• Collaborators: Atlantic Research Group
• Investigators: Study Director: Min-Fun Rudolf Kwan, MD, Kinex Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: September 18, 2013
• First Submitted That Met QC Criteria: October 17, 2013
• First Posted (Estimate): October 22, 2013

Study Record Updates

• Last Update Posted (Estimate): December 16, 2016
• Last Update Submitted That Met QC Criteria: December 15, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ORAX-01-13-US

Plan for Individual participant data (IPD)

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