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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 402
- 试验地点
- 44
- 主要终点
- Tumor response as determined by response criteria
研究概览
简要总结
To determine the safety and tolerability of Oraxol as compared to IV paclitaxel in metastatic breast cancer
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Oraxol (paclitaxel + HM30181AK-US)
Oraxol paclitaxel - supplied as 30-mg capsules
Oraxol HM30181 methansulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets
干预措施: Oraxol (Drug)
IV paclitaxel
IV paclitaxel - supplied as Taxol or generic
干预措施: IV paclitaxel (Drug)
结局指标
主要结局
Tumor response as determined by response criteria
时间窗: 19 to 22 weeks
Tumor response is evaluated using the response evaluation criteria in solid tumors (RECIST v1.1 criteria).
Safety and tolerability assessments of Oraxol compared with IV paclitaxel, as determined by laboratory, adverse event (AE) and serious adverse event (SAE) information
时间窗: 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).]
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
次要结局
- Overall survival (OS)(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).)
- Progression-free survival (PFS)(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).)