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

NCT ID: NCT02594371

Last Updated: 2022-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 402 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-02
• Study Completion Date: 2022-06-30

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).

Conditions

Metastatic Breast Cancer

Study Design

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

Study Groups

Oraxol (paclitaxel + HM30181AK-US)

Oraxol paclitaxel - supplied as 30-mg capsules

Oraxol HM30181 methansulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets

Group Type: EXPERIMENTAL

Oraxol

Intervention Type: DRUG

IV paclitaxel

IV paclitaxel - supplied as Taxol or generic

Group Type: ACTIVE_COMPARATOR

IV paclitaxel

Intervention Type: DRUG

Interventions

Oraxol

Intervention Type: DRUG

IV paclitaxel

Intervention Type: DRUG

Other Intervention Names

HM30181 methanesulfonate monohydrate; Oral paclitaxel capsules

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

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

Sponsors

Athenex, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Cutler, MD

Role: STUDY_DIRECTOR

Kinex Pharmaceuticals Inc.

Locations

Centro de Investigacion Pergamino SA

Pergamino, Buenos Aires, Argentina

Clinica Universitaria Privada Reina Fabiola

Córdoba, Córdoba Province, Argentina

IONC

Córdoba, Córdoba Province, Argentina

Centro Oncologico Infinito

Santa Rosa, La Pampa Province, Argentina

Fundación Koriza

Santa Rosa, La Pampa Province, Argentina

Clinica Viedma

Viedma, Río Negro Province, Argentina

CEMEDIC

Buenos Aires, , Argentina

COIBA

Buenos Aires, , Argentina

Fundación Investigar

Buenos Aires, , Argentina

Fundación Centro Oncológico Riojano Integral (CORI)

La Rioja, , Argentina

CAIPO

San Miguel de Tucumán, , Argentina

Centro Medico San Roque

San Miguel de Tucumán, , Argentina

Hospital Provincial del Centenario

Santa Fe, , Argentina

Instituto de Oncologia de Rosario

Santa Fe, , Argentina

Sanatorio Britanico

Santa Fe, , Argentina

Fundación Arturo López Pérez

Santiago, , Chile

Hospital de Referencia de Salud Cordillera Unidad de Patología Mamaria

Santiago, , Chile

Hospital San Borja Arriarán

Santiago, , Chile

IRAM

Santiago, , Chile

Clínica Alemana Temuco

Temuco, , Chile

Instituto Nacional de Cancerología E.S.E.

Bogotá, , Colombia

Fundación Colombiana de Cancerología Clinica Vida

Medellín, , Colombia

Fundación Hospitalaria San Vicente de Paúl

Medellín, , Colombia

Hemato Oncologos S.A.

Valle, , Colombia

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, , Dominican Republic

Hospital SOLCA

Guayaquil, , Ecuador

Hospital Carlos Andrade Martín

Quito, , Ecuador

Hospital SOLCA

Quito, , Ecuador

Espemedic

San Salvador, , El Salvador

Hospital Diagnotico Clinica Oncologica & Cancer Research

San Salvador, , El Salvador

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, , Guatemala

Excel Medica

Cortés, , Honduras

Tecnología en Investigación

Cortés, , Honduras

Centro Hemato Oncológico Panamá

Panama City, , Panama

Clínica Oncológica Miraflores

Lima, , Peru

Hospital Cayetano Heredia

Lima, , Peru

Hospital Nacional del Arzobispo Loayza

Lima, , Peru

Countries

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

References

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.

Reference Type: DERIVED

PMID: 35858154 (View on PubMed)

Other Identifiers

KX-ORAX-001

Identifier Type: -

Identifier Source: org_study_id