A Study to Determine the Bioequivalence of Oraxol in Cancer Patients Treated With Intravenous Paclitaxel

NCT ID: NCT04035473

Last Updated: 2022-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-01
• Study Completion Date: 2019-03-27

Brief Summary

This is a multicenter, open-label, 2-stage study with a 2-treatment period crossover design. Eligible participants are adults with cancer for whom weekly therapy with IV paclitaxel at a dose of 80 mg/m2 over 1 hour is indicated.

Stage 1 will consist of an initial cohort (Cohort 1) up to 6 evaluable participants who will receive a dosing regimen of Oraxol consisting of a 15-mg oral HM30181AK-US tablet plus an oral paclitaxel dose of 205 mg/m2, both administered once daily for 3 consecutive days. The stages and cohorts are further described in the "Study Design - Stages and Cohorts" table below. An interim analysis of pharmacokinetic (PK) data from Cohort 1 will be conducted to determine if the administered regimen would appear likely to achieve bioequivalence(BE) (AUC0-∞), if tested in a greater number of participants in Stage 2. If it appears unlikely that the selected regimen will meet the criteria for BE based on AUC0-∞ data, a second cohort (Cohort 2) of up to 6 evaluable participants may be enrolled in Stage 1, and the dose of paclitaxel in Oraxol may be adjusted by a maximum of +/- 25%. If Cohort 2 is enrolled, a second interim analysis will be conducted.

After the interim analysis/analyses (depending on the outcomes), a decision will be made by consensus of the Data Safety and Monitoring Board(DSMB), Kinex, Zenith Technology, and the Principal Investigator as to what dose should be administered in Stage 2. The DSMB will consist of a clinical oncologist, an ethicist, an independent statistician, and additional members, as deemed necessary. A DSMB charter will describe the planned evaluations and decision points used to determine the dose for Stage 2. An additional 18 to 42 evaluable participants will be enrolled into Stage 2 based on the Stage 1 results (AUC0-∞). Thus a total of up to 54 evaluable participants could potentially be enrolled in this study (6 each from Stage 1, Cohorts 1 and 2, and up to 42 participants in Stage 2).

Detailed Description

Stage 1 will consist of an initial cohort (Cohort 1) up to 6 evaluable participants who will receive a dosing regimen of Oraxol consisting of a 15-mg oral HM30181AK-US tablet plus an oral paclitaxel dose of 205 mg/m2, both administered once daily for 3 consecutive days. The stages and cohorts are further described in the "Study Design - Stages and Cohorts" table below. An interim analysis of pharmacokinetic (PK) data from Cohort 1 will be conducted to determine if the administered regimen would appear likely to achieve bioequivalence (BE) (AUC0-∞), if tested in a greater number of participants in Stage 2. If it appears unlikely that the selected regimen will meet the criteria for BE based on AUC0-∞ data, a second cohort (Cohort 2) of up to 6 evaluable participants may be enrolled in Stage 1, and the dose of paclitaxel in Oraxol may be adjusted by a maximum of +/- 25%. If Cohort 2 is enrolled, a second interim analysis will be conducted.

After the interim analysis/analyses (depending on the outcomes), a decision will be made by consensus of the Data Safety and Monitoring Board(DSMB), Kinex, Zenith Technology, and the Principal Investigator as to what dose should be administered in Stage 2. The DSMB will consist of a clinical oncologist, an ethicist, an independent statistician, and additional members, as deemed necessary. A DSMB charter will describe the planned evaluations and decision points used to determine the dose for Stage 2. An additional 18 to 42 evaluable participants will be enrolled into Stage 2 based on the Stage 1 results (AUC0-∞). Thus a total of up to 54 evaluable participants could potentially be enrolled in this study (6 each from Stage 1, Cohorts 1 and 2, and up to 42 participants in Stage 2).

Conditions

Solid Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sequence A (Oraxol, IV paclitaxel)

The treatment sequences will be:

A Oraxol (paclitaxel + HM30181) on Days 1, 2, and 3 of Treatment Period 1 followed by IV paclitaxel on Day 1 of Treatment Period 2 B IV paclitaxel on Day 1 of Treatment Period 1 followed by Oraxol on Days 1, 2, and 3 of Treatment Period 2

Group Type: ACTIVE_COMPARATOR

HM30181 methanesulfonate monohydrate plus oral paclitaxel capsules

Intervention Type: DRUG

HM30181 methanesulfonate monohydrate plus oral paclitaxel capsules

Oral paclitaxel capsules

Sequence B (IV paclitaxel, Oraxol)

The treatment sequences will be:

A IV paclitaxel on Day 1 of Treatment Period 1 followed by Oraxol on Days 1, 2, and 3 of Treatment Period 2 B Oraxol (paclitaxel + HM30181) on Days 1, 2, and 3 of Treatment Period 1 followed by IV paclitaxel on Day 1 of Treatment Period 2

Group Type: ACTIVE_COMPARATOR

HM30181 methanesulfonate monohydrate plus oral paclitaxel capsules

Intervention Type: DRUG

HM30181 methanesulfonate monohydrate plus oral paclitaxel capsules

Oral paclitaxel capsules

Interventions

HM30181 methanesulfonate monohydrate plus oral paclitaxel capsules

HM30181 methanesulfonate monohydrate plus oral paclitaxel capsules

Oral paclitaxel capsules

Intervention Type: DRUG

Other Intervention Names

ORAXOL

Eligibility Criteria

Inclusion Criteria

1. Signed written informed consent

2. Males and females ≥18 years of age on day of consent

3. Cancer patients for whom treatment with IV paclitaxel at 80 mg/m2has been recommended by their oncologist, either as monotherapy or in combination with other agents

4. Adequate hematologic status at Screening/Baseline:

• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Platelet count ≥100 x 109/L
• Hemoglobin (Hgb) ≥90 g/L

5. Adequate liver function at Screening/Baseline 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

6. Adequate renal function at Screening/Baseline as demonstrated by serum creatinine ≤177 μmol/L or creatinine clearance >50 mL/min as calculated by the Cockcroft and Gault formula

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 16

8. Life expectancy of at least 3 months

9. Willing to fast for 8 hours before and 4 hours after Oraxol administration

10. Willing to abstain from alcohol consumption for 3 days before the first dose of study drug through the completion of protocol-specified PK sampling in Treatment Period 2

11. Willing to refrain from caffeine consumption for 12 hours before each treatment period through the completion of protocol-specified PK sampling for that dose

12. Women must be postmenopausal (>12 months without menses) or surgically sterile (ie, by hysterectomy and/or bilateral oophorectomy) or, if sexually active, must be using effective contraception (ie, oral contraceptives, intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for the duration of their participation in the study. Women of childbearing potential must agree to use contraception for 30 days after their last dose of study drug.

13. Sexually active male participants must use a barrier method of contraception during the study and agree to continue the use of male contraception for at least 30 days after the last dose of study drug.

Exclusion Criteria

1. 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)
• Known P-glycoprotein (P-gp) inhibitors or inducers. 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 PK sampling after the administration of the second 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

2. 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.

3. Unresolved toxicity from prior chemotherapy (participants must have recovered all significant toxicity to ≤ Grade 1 CTCAE toxicity1 from previous anticancer treatments or previous investigational agents). This does not extend to symptoms or findings that are attributable to the underlying disease

4. Received investigational agents within 14 days or 5 half-lives prior to the first study dosing day, whichever is longer

5. Women of childbearing potential who are pregnant or breastfeeding

6. 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

7. 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

8. 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.

9. Any other condition which the Investigator believes would make a subject's participation in the study not acceptable

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaEssentia

INDUSTRY

Sponsor Role: collaborator

Zenith Technology Corporation Limited

INDUSTRY

Sponsor Role: collaborator

Athenex, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Cutler, MD

Role: STUDY_DIRECTOR

Athenex, Inc.

Locations

Monash Medical Centre

Melbourne, , Australia

Auckland City Hospital

Auckland, , New Zealand

Dunedin Hospital

Dunedin, , New Zealand

Wellington Regional Hospital

Wellington, , New Zealand

Shuang Ho hospital

New Taipei City, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Lotung Poh-Ai Hospital

Yilan, , Taiwan

Countries

Australia; New Zealand; Taiwan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

KX-ORAX-002

Identifier Type: -

Identifier Source: org_study_id