A Safety Study of Oraxol (HM30181 + Oral Paclitaxel) in Cancer Patients

NCT04180384 | Completed Phase 2

• 1 other identifier: KX-ORAX-003
• Study Type: interventional
• Target: 44
• Locations: 4 countries
• Sites: 8

Brief Summary

Oraxol is a combination of an oral tablet, HM30181 methanesulfonate, and capsules that contain paclitaxel. HM30181 is a drug that helps the body absorb paclitaxel, a drug used to treat cancer. Initially this study is intended as an extension study of KX-ORAX-002 pharmacokinetic study for patients who wish to continue Oraxol treatment and who are eligible to participate. The purpose of this study is to check the safety and tolerability of Oraxol when it is administered on a weekly basis and to confirm the sustained oral bioavailability of paclitaxel following multiple dosing; also compare the relative bioavailability of paclitaxel tablets vs paclitaxel capsules (Group B only).

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of Oraxol (Incidence of Treatment-Emergent Adverse Events)

  Safety and tolerability as assessed by the incidence of adverse events. Treatment-emergent AEs (TEAEs) are defined as those AEs with an onset after dosing and those pre-existing AEs that worsen during the study. AEs will include those reported by participants as well as those observed by the clinical team, or clinically significant changes in lab tests, vital signs and ECGs. Possible AEs may include gastrointestinal effects and abdominal pain but as this is an early phase clinical trial and the likely AE profile is not yet known.

  From screening until final visit (within 28 days after the last dose of study drug was taken, and preferably before the participant receives any additional chemotherapy).

Secondary Outcomes (2)

• Sustained oral bioavailability of paclitaxel following multiple dosing

  PK samples will be collected during dosing for Week 4 or may be done during a later dosing week at the investigator's discretion and/or at the participant's convenience before patients' withdrawal from the study, up to 8 months.

• the relative bioavailability of paclitaxel tablets vs paclitaxel capsules (Group B only)

  PK samples will be collected during dosing for Week 5; or may be done during a later dosing week at the investigator's discretion and/or at the participant's convenience, up to 8 months.

Study Arms (2)

Oraxol (paclitaxel capsules+ HM30181AK-US)

EXPERIMENTAL

Oraxol paclitaxel - supplied as 30-mg capsules Oraxol HM30181 methansulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets

Drug: Oraxol

Oraxol (paclitaxel tablets+ HM30181AK-US)

ACTIVE COMPARATOR

Oraxol paclitaxel - supplied as 30-mg tablets Oraxol HM30181 methansulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets

Drug: Oraxol

Interventions

Oraxol DRUG

Paclitaxel: 5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13- ester with (2R,3S)-N-benzoyl-3-phenylisoserine HM30181 methanesulfonate monohydrate: N-(2-(2-(4-(2-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-2H-tetrazol-5-yl)-4,5-dimethoxyphenyl)-4-oxo-4H-chromene-2-carboxamide Methanesulfonate monohydrate

Also known as: HM30181 methanesulfonate monohydrate, Oral paclitaxel capsules, Oral paclitaxel tablets

Oraxol (paclitaxel capsules+ HM30181AK-US); Oraxol (paclitaxel tablets+ HM30181AK-US)

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
• Males and females ≥18 years of age on day of consent
• Cancer patients for whom treatment with IV paclitaxel at 80 mg/m2 has been recommended by their oncologist, either as monotherapy or in combination with other agents
• Adequate hematologic status:
• Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L
• Platelet count ≥100 x 10\^9/L
• Hemoglobin (Hgb) ≥90 g/L
• Adequate liver function as demonstrated by:
• Total bilirubin of ≤20 μmol/L or ≤30 μmol/L for participants with liver metastasis
• Alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN) or ≤5 x ULN if liver metastasis is present
• Alkaline phosphatase (ALP) ≤3 x ULN or ≤5 x ULN if liver or bone metastasis are present
• ALP \>5 x ULN if liver or bone metastasis are present and the major fraction of ALP is from bone metastasis, at the discretion of the Investigator
• Gamma glutamyl transferase (GGT) \<10 x ULN
• Adequate renal function as demonstrated by serum creatinine ≤177 μmol/L or creatinine clearance \>50 mL/min as calculated by the Cockcroft and Gault formula
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 16

You may not qualify if:

• Currently taking a prohibited concomitant medication:
• Strong inhibitors (eg, ketoconazole) or strong inducers (eg, rifampin or St. John's Wort) of cytochrome P450 (CYP) 3A4 (within 2 weeks prior to the start of dosing in the study)
• Strong inhibitors (eg, gemfibrozil) or strong inducers (eg, rifampin) of CYP2C8 (within 2 weeks prior to the start of dosing in the study)
• Strong P-gp inhibitors (eg, verapamil) or strong inducers (eg, rifampin). Participants who are taking such medications but who are otherwise eligible may be enrolled if they discontinue the medication ≥1 week before dosing and remain off that medication through the end of study treatment.
• An oral medication with a narrow therapeutic index known to be a P-gp substrate (eg, digoxin, dabigatran) within 24 hours prior to start of dosing in the study
• Use of warfarin. Participants receiving warfarin who are otherwise eligible and who may be appropriately managed with low molecular weight heparin, in the opinion of the Investigator, may be enrolled in the study provided they are switched to low molecular weight heparin at least 7 days prior to receiving study treatment.
• Unresolved toxicity from prior chemotherapy (participants must have recovered all significant toxicity to ≤ Grade 1 CTCAE toxicity from previous anticancer treatments or previous investigational agents). This does not extend to symptoms or findings that are attributable to the underlying disease
• Received investigational agents within 14 days or 5 half-lives prior to the first study dosing day, whichever is longer
• Women of childbearing potential who are pregnant or breastfeeding
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant myocardial infarction within the last 6 months, unstable angina pectoris, clinically significant cardiac arrhythmia, bleeding disorder, chronic pulmonary disease requiring oxygen, or psychiatric illness/social situations that would limit compliance with study requirements
• Major surgery to the upper 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
• A known history of allergy to paclitaxel. Participants whose allergy was due to the IV solvent (such as Cremophor®) and not paclitaxel will be eligible for this study.
• Any other condition which the Investigator believes would make a subject's participation in the study not acceptable

Sponsors & Collaborators

• Athenex, Inc.: lead
• Zenith Technology Corporation Limited: collaborator
• PharmaEssentia: collaborator

Study Sites (8)

Monash Medical Centre

Clayton, 3168, Australia

Location

Auckland City Hospital

Auckland, New Zealand

Location

Dunedin Hospital

Dunedin, New Zealand

Location

Wellington Regional Hospital

Wellington, New Zealand

Location

Taipei Medical University Shuang Ho Hospital

New Taipei City, 23561, Taiwan

Location

Tri-Service General Hospital

Taipei, 114, Taiwan

Location

Lotung Poh-Ai Hospital

Yilan, Taiwan

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Interventions

Paclitaxel

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jackson Christopher, MD

  Dunedin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: For 1 dosing week (at least 1 week following the paclitaxel capsule PK sampling period, ie, at Week 5 or later), a subgroup of 8 participants (Group B) will receive Oraxol as HM30181 plus a tablet formulation of paclitaxel. For the remainder of the study, Group B participants will receive the current clinical capsule formulation of paclitaxel. This will allow for comparison of the bioavailability of these 2 formulations with minimal impact on safety or activity.

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: November 27, 2019
• Study Start: September 23, 2015
• Primary Completion: June 15, 2021
• Study Completion: June 15, 2021
• Last Updated: July 29, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (3); GB (1); TW (3); AU (1)