A PK Study of Oraxol in Breast Cancer Patients

NCT04993040 | Completed Phase 1 FDA Drug

• 1 other identifier: KX-ORAX-CN-007
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open-label, single-arm PK study in approximately 24 breast cancer patients for whom paclitaxel treatment is indicated.

Conditions

Breastcancer

Keywords

breast cancer; paclitaxel

Outcome Measures

Primary Outcomes (5)

• Cmax

  Plasma concentrations for paclitaxel only will be analyzed to determine the maximum observed concentration (Cmax). Pharmacokinetic parameters will be summarized using the mean, standard deviation, median, minimum, and maximum. Summaries of PK parameters will also include the geometric mean and the coefficient of variation. Summary PK and individual timepoints will be tabulated and displayed graphically and listed for all subjects.

  Week 1 (Days 1,2, 3): Predose, and at 1, 2, 3, and 4 hours postdose; Week 4 (Days 1,2,3): Predose, and at 1, 2, 3, and 4 hours postdose

• Cmin

  Plasma concentrations for paclitaxel only will be analyzed to determine the minimum observed concentration (Cmin). Pharmacokinetic parameters will be summarized using the mean, standard deviation, median, minimum, and maximum. Summaries of PK parameters will also include the geometric mean and the coefficient of variation. Summary PK and individual timepoints will be tabulated and displayed graphically and listed for all subjects.

  Week 1 (Days 1,2, 3): Predose, and at 1, 2, 3, and 4 hours postdose; Week 4 (Days 1,2,3): Predose, and at 1, 2, 3, and 4 hours postdose

• Cavg

  Plasma concentrations for paclitaxel only will be analyzed to determine the area under the curve extrapolated to infinity (AUC0-t). Pharmacokinetic parameters will be summarized using the mean, standard deviation, median, minimum, and maximum. Summaries of PK parameters will also include the geometric mean and the coefficient of variation. Summary PK and individual timepoints will be tabulated and displayed graphically and listed for all subjects.

  Week 1 (Days 1,2, 3): Predose, and at 1, 2, 3, and 4 hours postdose; Week 4 (Days 1,2,3): Predose, and at 1, 2, 3, and 4 hours postdose

• AUC0-t

  Plasma concentrations for paclitaxel only will be analyzed to determine the area under the curve (AUC). Pharmacokinetic parameters will be summarized using the mean, standard deviation, median, minimum, and maximum. Summaries of PK parameters will also include the geometric mean and the coefficient of variation. Summary PK and individual timepoints will be tabulated and displayed graphically and listed for all subjects.

  Week 1 (Days 1,2, 3): Predose, and at 1, 2, 3, and 4 hours postdose; Week 4 (Days 1,2,3): Predose, and at 1, 2, 3, and 4 hours postdose

• AUC

  Plasma concentrations for paclitaxel only will be analyzed to determine the area under the curve (AUC). Pharmacokinetic parameters will be summarized using the mean, standard deviation, median, minimum, and maximum. Summaries of PK parameters will also include the geometric mean and the coefficient of variation. Summary PK and individual timepoints will be tabulated and displayed graphically and listed for all subjects.

  Week 1 (Days 1,2, 3): Predose, and at 1, 2, 3, and 4 hours postdose; Week 4 (Days 1,2,3): Predose, and at 1, 2, 3, and 4 hours postdose

Secondary Outcomes (4)

• Safety

  From screening until final visit (within within 7 days after last dose of study treatment)

• Tumor response rate

  From screening until final visit (within within 7 days after last dose of study treatment)

• Progression-free survival

  From date of dosing until the date of first documented progression or date of death from any cause, whichever came first, estimated up to 24 months

• Overall survival

  From date of dosing until the date of death from any cause, whichever came first, estimated up to 24 months

Study Arms (1)

Oraxol

EXPERIMENTAL

Subjects will receive Oraxol 205 mg/m2 daily x 3 days weekly for up to 16 weeks.

Drug: Oraxol

Interventions

Oraxol DRUG

* HM30181 methanesulfonate monohydrate * Oral paclitaxel capsules

Also known as: HM30181 methanesulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets, Paclitaxel - supplied as 30-mg capsules

Oraxol

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent
• Women ≥18 years of age on day of consent
• Breast cancer in patients for whom treatment with IV paclitaxel at 80 mg/m2 as monotherapy has been recommended by their oncologist.
• Measurable disease as per RECIST v1.1 criteria
• Adequate hematological status as demonstrated by not requiring transfusion support or granulocyte-colony stimulating factor (G-CSF) to maintain:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Platelet count ≥100 x 109/L
• Hemoglobin (Hgb) ≥9 g/dL
• Adequate liver function as demonstrated by:
• Total bilirubin of ≤1.5 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤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 bone metastasis is present
• Gamma glutamyl transferase (GGT) \<10 x ULN
• Adequate renal function as demonstrated by serum creatinine ≤1.5 x ULN
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

• Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous investigational products (IPs)
• If previously treated with a taxane (paclitaxel or docetaxel) as part of anthracycline-based adjuvant chemotherapy or for metastatic disease, the subject relapsed less than 1 year following treatment
• Subjects unable to swallow study medication in its intact form or have clinically significant malabsorption syndrome
• Only site of metastatic disease is unmeasurable according to RECIST v1.1 criteria
• Known CNS metastasis, including leptomeningeal involvement
• Received IPs within 14 days or 5 half-lives of the first study dosing day, whichever is longer
• Are currently receiving other medications intended for the treatment of their malignancy
• Women who are pregnant or breastfeeding
• Taking any of the following prohibited medications:
• Strong inhibitors (eg, ketoconazole) or inducers (eg, rifampin or St. John's Wort) of CYP3A4 (within 2 weeks prior to the start of dosing in the study)
• Strong inhibitors (eg, gemfibrozil) or inducers (eg, rifampin) of CYP2C8 (within 2 weeks prior to the start of dosing in the study)
• Strong P-gp inhibitors or inducers. Subjects 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. Subjects 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.
• 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 any concomitant illness or social situation that would limit compliance with study requirements

Sponsors & Collaborators

• Athenex, Inc.: lead

Study Sites (1)

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510000, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Erwei Song, Pro.f

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

• Herui Yao, Pro.f

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: August 6, 2021
• Study Start: April 22, 2019
• Primary Completion: December 9, 2019
• Study Completion: December 9, 2020
• Last Updated: August 6, 2021

Record last verified: 2021-02

Locations

CN (1)