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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02594371
• Other study ID #: KX-ORAX-001
• Status: Completed
• Phase: Phase 3
• Start date: December 2, 2015
• Est. completion date: June 30, 2022

Study information

• Verified date: August 2022
• Source: Athenex, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 402
• Est. completion date: June 30, 2022
• Est. primary completion date: July 25, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Oraxol

• IV paclitaxel

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Athenex, Inc.

Countries where clinical trial is conducted

Argentina,  Chile,  Colombia,  Dominican Republic,  Ecuador,  El Salvador,  Guatemala,  Honduras,  Panama,  Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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).
Secondary	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).