Clinical trial NCT02594371: Ph3 Study To Determine Safety,Tolerability&Tumor Response Of Oraxol Compared To Taxol In Metastatic Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Lead sponsor: Athenex, Inc.
Sponsor class: INDUSTRY
First posted: 2015-11-03
Enrollment: 402
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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).

Eligibility criteria: 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

Primary outcomes:
measure: Tumor response as determined by response criteria
timeFrame: 19 to 22 weeks
measure: Safety and tolerability assessments of Oraxol compared with IV paclitaxel, as determined by laboratory, adverse event (AE) and serious adverse event (SAE) information
timeFrame: 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 outcomes:
measure: Progression-free survival (PFS)
timeFrame: 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).
measure: Overall survival (OS)
timeFrame: 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).
Other outcomes:
Locations:
city: Pergamino
country: Argentina
facility: Centro de Investigacion Pergamino SA
state: Buenos Aires
city: Ciudad de Córdoba
country: Argentina
facility: IONC
state: Cordoba
city: Córdoba
country: Argentina
facility: Clinica Universitaria Privada Reina Fabiola
state: Cordoba
city: Santa Rosa
country: Argentina
facility: Centro Oncologico Infinito
state: La Pampa
city: Santa Rosa
country: Argentina
facility: Fundación Koriza
state: La Pampa
city: Viedma
country: Argentina
facility: Clinica Viedma
state: Rio Negro
city: Buenos Aires
country: Argentina
facility: COIBA
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: CEMEDIC
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Fundación Investigar
city: La Rioja
country: Argentina
facility: Fundación Centro Oncológico Riojano Integral (CORI)
city: Santa Fe
country: Argentina
facility: Hospital Provincial del Centenario
city: Santa Fe
country: Argentina
facility: Instituto de Oncologia de Rosario
city: Santa Fe
country: Argentina
facility: Sanatorio Britanico
city: Tucuman
country: Argentina
facility: Centro Medico San Roque
city: Tucumán
country: Argentina
facility: CAIPO
city: Santiago de Chile
country: Chile
facility: Fundación Arturo López Pérez
city: Santiago de Chile
country: Chile
facility: Hospital de Referencia de Salud Cordillera Unidad de Patología Mamaria
city: Santiago de Chile
country: Chile
facility: Hospital San Borja Arriarán
city: Santiago de Chile
country: Chile
facility: IRAM
city: Temuco
country: Chile
facility: Clínica Alemana Temuco
city: Bogota
country: Colombia
facility: Instituto Nacional de Cancerología E.S.E.
city: Medellín
country: Colombia
facility: Fundación Colombiana de Cancerología Clinica Vida
city: Medellín
country: Colombia
facility: Fundación Hospitalaria San Vicente de Paúl
city: Valle
country: Colombia
facility: Hemato Oncologos S.A.
city: Santiago de los Caballeros
country: Dominican Republic
facility: Hospital Metropolitano de Santiago (HOMS)
city: Santo Domingo
country: Dominican Republic
facility: Clinical Research
city: Santo Domingo
country: Dominican Republic
facility: Hospital General de la Plaza de la Salud
city: Guayaquil
country: Ecuador
facility: Hospital SOLCA
city: Quito
country: Ecuador
facility: Hospital Carlos Andrade Martín
city: Quito
country: Ecuador
facility: Hospital SOLCA
city: San Salvador
country: El Salvador
facility: Espemedic
city: San Salvador
country: El Salvador
facility: Hospital Diagnotico Clinica Oncologica & Cancer Research
city: Guatemala City
country: Guatemala
facility: American Cancer Center
city: Guatemala City
country: Guatemala
facility: CELAN Clínica Médica
city: Guatemala city
country: Guatemala
facility: Clinica Privada
city: Guatemala City
country: Guatemala
facility: Clínica Privada
city: Guatemala City
country: Guatemala
facility: Grupo Angeles, S.A.
city: Guatemala City
country: Guatemala
facility: Oncomedica en Guatemala
city: Quetzaltenango
country: Guatemala
facility: CRESEM
city: Cortés
country: Honduras
facility: Excel Medica
city: Cortés
country: Honduras
facility: Tecnología en Investigación
city: Panama city
country: Panama
facility: Centro Hemato Oncológico Panamá
city: Lima
country: Peru
facility: Clínica Oncológica Miraflores
city: Lima
country: Peru
facility: Hospital Cayetano Heredia
city: Lima
country: Peru
facility: Hospital Nacional del Arzobispo Loayza
Study officials:
affiliation: Kinex Pharmaceuticals Inc.
name: David Cutler, MD
role: STUDY_DIRECTOR
References:
citation: 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. 2023 Jan 1;41(1):65-74. doi: 10.1200/JCO.21.02953. Epub 2022 Jul 20.