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

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

Detailed Description
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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).

Official Title
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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

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Oraxol
* Drug: IV paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Women ≥18 years of age Histologically- or cytologically-confirmed breast cancer for whom IV paclitaxel (as Taxol or generic) monotherapy has been recommended by their oncologist Measurable metastatic target lesion disease measurable by CT scan as per RECIST v1.1 criteria 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 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 Adequate renal function as demonstrated by serum creatinine ≤1.5 x ULN Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy of at least 6 months, in the judgement of the investigator 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. Subjects who are of childbearing potential must have a negative screening serum pregnancy test. Exclusion Criteria: Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous investigational products 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 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 Central nervous system 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 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 Women who are pregnant or breastfeeding Taking a medication known to be a strong P-gp inhibitor or inducer within 14 days of starting treatment Taking an oral medication with a narrow therapeutic index known to be a P-gp substrate within 24 hours prior to start of treatment 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 Taking a medication known to be a strong inhibitor (eg, gemfibrozil) or inducer (eg, rifampin) of CYP2C8 within 14 days of starting 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 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 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 Known allergic reaction or intolerance to contrast media Documented history of true systemic allergic reaction to 3 or more medications For whom the Investigator believes that participation in this study would not be acceptable Known chronic hepatitis or cirrhosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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). |