Ph3 Study To Determine Safety,Tolerability&Tumor Response Of Oraxol Compared To Taxol In Metastatic Breast Cancer

An Open-Label, Randomized, Multicenter, Phase 3 Study to Determine the Safety, Tolerability, and Tumor Response of Oraxol and Its Comparability to IV Taxol or Generic IV Paclitaxel in Subjects With Metastatic Breast Cancer

To determine the safety and tolerability of Oraxol as compared to IV paclitaxel in metastatic breast cancer

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Oraxol; Drug: IV paclitaxel

Detailed Description

This is a Phase 3, open-label, randomized, multicenter study in approximately 360 adult female subjects with histologically- or cytologically-confirmed breast cancer that is metastatic for whom treatment with IV paclitaxel monotherapy has been recommended by their oncologist. Approximately 400 subjects will be enrolled to provide 360 evaluable subjects. The subjects must have measurable metastatic target lesion disease as per RECIST v1.1 criteria. Subjects will be randomized in a 2:1 ratio to either Oraxol or IV paclitaxel (as Taxol or generic).

• Study Type: Interventional
• Enrollment (Actual): 402
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • COIBA
  • Ciudad Autónoma de Buenos Aires, Argentina
    • CEMEDIC
  • Ciudad Autónoma de Buenos Aires, Argentina
    • Fundación Investigar
  • La Rioja, Argentina
    • Fundación Centro Oncológico Riojano Integral (CORI)
  • Santa Fe, Argentina
    • Hospital Provincial del Centenario
  • Santa Fe, Argentina
    • Instituto de Oncología de Rosario
  • Santa Fe, Argentina
    • Sanatorio Britanico
  • Tucuman, Argentina
    • Centro Medico San Roque
  • Tucumán, Argentina
    • CAIPO
  • Buenos Aires
    • Pergamino, Buenos Aires, Argentina
      • Centro de Investigacion Pergamino SA
  • Cordoba
    • Ciudad de Córdoba, Cordoba, Argentina
      • IONC
    • Córdoba, Cordoba, Argentina
      • Clínica Universitaria Privada Reina Fabiola
  • La Pampa
    • Santa Rosa, La Pampa, Argentina
      • Centro Oncologico Infinito
    • Santa Rosa, La Pampa, Argentina
      • Fundacion Koriza
  • Rio Negro
    • Viedma, Rio Negro, Argentina
      • Clínica Viedma
• Chile
  • Santiago de Chile, Chile
    • Fundacion Arturo Lopez Perez
  • Santiago de Chile, Chile
    • Hospital de Referencia de Salud Cordillera Unidad de Patología Mamaria
  • Santiago de Chile, Chile
    • Hospital San Borja Arriarán
  • Santiago de Chile, Chile
    • IRAM
  • Temuco, Chile
    • Clínica Alemana Temuco
• Colombia
  • Bogota, Colombia
    • Instituto Nacional de Cancerologia E.S.E.
  • Medellín, Colombia
    • Fundacion Colombiana de Cancerologia Clinica Vida
  • Medellín, Colombia
    • Fundación Hospitalaria San Vicente de Paul
  • Valle, Colombia
    • Hemato Oncologos S.A.
• Dominican Republic
  • Santiago de los Caballeros, Dominican Republic
    • Hospital Metropolitano de Santiago (HOMS)
  • Santo Domingo, Dominican Republic
    • Clinical research
  • Santo Domingo, Dominican Republic
    • Hospital General de la Plaza de la Salud
• Ecuador
  • Guayaquil, Ecuador
    • Hospital SOLCA
  • Quito, Ecuador
    • Hospital Carlos Andrade Martín
  • Quito, Ecuador
    • Hospital SOLCA
• El Salvador
  • San Salvador, El Salvador
    • Espemedic
  • San Salvador, El Salvador
    • Hospital Diagnotico Clinica Oncologica & Cancer Research
• Guatemala
  • Guatemala City, Guatemala
    • American Cancer Center
  • Guatemala City, Guatemala
    • CELAN Clínica Médica
  • Guatemala City, Guatemala
    • Clinica privada
  • Guatemala City, Guatemala
    • Grupo Angeles, S.A.
  • Guatemala City, Guatemala
    • Oncomedica en Guatemala
  • Guatemala city, Guatemala
    • Clinica privada
  • Quetzaltenango, Guatemala
    • CRESEM
• Honduras
  • Cortés, Honduras
    • Excel Medica
  • Cortés, Honduras
    • Tecnología en Investigación
• Panama
  • Panama city, Panama
    • Centro Hemato Oncologico Panama
• Peru
  • Lima, Peru
    • Clínica Oncológica Miraflores
  • Lima, Peru
    • Hospital Cayetano Heredia
  • Lima, Peru
    • Hospital Nacional del Arzobispo Loayza

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed written informed consent
2. Women ≥18 years of age
3. Histologically- or cytologically-confirmed breast cancer for whom IV paclitaxel (as Taxol or generic) monotherapy has been recommended by their oncologist
4. Measurable metastatic target lesion disease measurable by CT scan as per RECIST v1.1 criteria

5. Adequate hematological status as demonstrated by not requiring granulocyte-colony stimulating factor (G-CSF) or transfusion support to achieve the following at Screening:

   • Absolute neutrophil count (ANC) ≥1.5 x 109/L
   • Platelet count ≥100 x 109/L
   • Hemoglobin ≥10 g/dL

6. Adequate liver function as demonstrated by:

   • Total bilirubin within normal limits (WNL)
   • Alanine aminotransferase and aspartate aminotransferase ≤3 x upper limit of normal (ULN)
   • Alkaline phosphatase ≤3 x ULN or ≤5 x ULN if bone metastasis is present
   • Gamma glutamyl transferase (GGT) ≤5 x ULN
7. Adequate renal function as demonstrated by serum creatinine ≤1.5 x ULN
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9. Life expectancy of at least 6 months, in the judgement of the investigator
10. Subjects must be postmenopausal (≥12 months without menses) or surgically sterile (ie, by hysterectomy and/or bilateral oophorectomy) or must be using effective contraception and agree to used of contraception for 30 days after their last dose of assigned study treatment.
11. Subjects who are of childbearing potential must have a negative screening serum pregnancy test.

Exclusion Criteria:

1. Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous investigational products
2. 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
3. Only evidence of metastatic disease is to bone or other nontarget or nonmeasurable lesions (including, for example, ascites or plural effusion) according to RECIST v1.1 criteria
4. Central nervous system metastasis, including leptomeningeal involvement
5. Received IPs within 14 days or 5 half-lives of the first study dosing day, whichever is longer
6. Are currently receiving other medications intended for the treatment of their malignancy
7. Received radiation therapy within 2 weeks prior to signing informed consent and those for whom radiation therapy is planned within 6 months from the time of signing informed consent
8. Women who are pregnant or breastfeeding
9. Taking a medication known to be a strong P-gp inhibitor or inducer within 14 days of starting treatment
10. Taking an oral medication with a narrow therapeutic index known to be a P-gp substrate within 24 hours prior to start of treatment
11. Taking a medication known to be a strong cytochrome P450 (CYP) 3A4 inhibitor (eg, ketoconazole) or inducer (eg, rifampin or St. John's Wort) within 14 days of starting treatment
12. Taking a medication known to be a strong inhibitor (eg, gemfibrozil) or inducer (eg, rifampin) of CYP2C8 within 14 days of starting treatment
13. 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
14. 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
15. History of significant hypersensitivity-type reactions to paclitaxel or Cremophor EL (polyoxyl 35 castor oil, NF) that would contraindicate the use of IV paclitaxel formulated with Cremophor EL
16. Known allergic reaction or intolerance to contrast media
17. Documented history of true systemic allergic reaction to 3 or more medications
18. For whom the Investigator believes that participation in this study would not be acceptable
19. Known chronic hepatitis or cirrhosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oraxol (paclitaxel + HM30181AK-US); Oraxol paclitaxel - supplied as 30-mg capsules Oraxol HM30181 methansulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets	Drug: Oraxol; Other Names: HM30181 methanesulfonate monohydrate; Oral paclitaxel capsules
Active Comparator: IV paclitaxel; IV paclitaxel - supplied as Taxol or generic	Drug: IV paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response as determined by response criteria	Tumor response is evaluated using the response evaluation criteria in solid tumors (RECIST v1.1 criteria).	19 to 22 weeks
Safety and tolerability assessments of Oraxol compared with IV paclitaxel, as determined by laboratory, adverse event (AE) and serious adverse event (SAE) information	Safety assessments will consist of determining and recording all AEs and SAEs; laboratory evaluation of hematology, blood chemistry, and urine analyses; periodic measurement of vital signs and electrocardiograms (ECGs); and the performance of physical examinations, as detailed in the schedule of procedures and assessments of the protocol	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to ~48 months (expected end of study).]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	The endpoint of progression-free survival is defined as not having died or progression of disease. Lost to follow-up will be considered as censored.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to ~48 months (expected end of study).
Overall survival (OS)	The endpoint of overall survival is defined as death, confirmed alive, and lost to follow-up. Alive and lost to follow-up will be considered as censored.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to ~48 months (expected end of study).

Collaborators and Investigators

• Sponsor: Athenex, Inc.
• Investigators: Study Director: David Cutler, MD, Kinex Pharmaceuticals Inc.

Publications and helpful links

General Publications

• Rugo HS, Umanzor GA, Barrios FJ, Vasallo RH, Chivalan MA, Bejarano S, Ramirez JR, Fein L, Kowalyszyn RD, Kramer ED, Wang H, Kwan MR, Cutler DL; Oraxol Study Consortium Investigators. Open-Label, Randomized, Multicenter, Phase III Study Comparing Oral Paclitaxel Plus Encequidar Versus Intravenous Paclitaxel in Patients With Metastatic Breast Cancer. J Clin Oncol. 2022 Jul 20:JCO2102953. doi: 10.1200/JCO.21.02953. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2015
• Primary Completion (Actual): July 25, 2019
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: October 28, 2015
• First Submitted That Met QC Criteria: October 30, 2015
• First Posted (Estimate): November 3, 2015

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: KX-ORAX-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No