Phase Ib/II Trials of RAD001 in Triple Negative Metastatic Breast Cancer
A Phase Ib Trial of Gemcitabine and Cisplatin With RAD001 in Patients With Metastatic Triple Negative Breast Cancer Proceeding to an Open Label Randomized Phase II Trial Comparing Gemcitabine/Cisplatin With or Without RAD001.
研究概览
详细说明
PIK3CA active mutations are the most frequent genetic event in breast cancer, including in TNBC which presents activated PI3K/AKT signaling due to PIK3CA mutation or PTEN deficiency. TNBC cell lines having activated PI3K/AKT signaling showed a high sensitivity to PI3K/mTOR inhibitors. RAD001 is a potent mTOR complex 1 inhibitor and showed to enhance cisplatin or gemcitabine induced apoptosis by inhibiting p53 induced p21 expression.
This study consists of two parts. In a phase Ib part, investigators will explore the recommended dose of gemcitabine, cisplatin, and RAD001 combination in patients with metastatic TNBC. After completing the phase Ib part, investigators will review the data and discuss with Novartis before the start of a phase II part. In the phase II part, investigators will compare the efficacy of the gemcitabine and cisplatin with or without RAD001 in patients with metastatic TNBC.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Gyeonggido
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Goyangsi、Gyeonggido、大韩民国、410-769
- National Cancer Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Females with histologically confirmed, metastatic or stage IV breast cancer
- ER/PgR negative or poor (Allred score ≤ 3/8) and HER2 negative breast cancer
- ECOG performance status 0-2
- Age ≥ 20 years
- Previously treated by anthracycline and taxane in adjuvant/neoadjuvant or metastatic setting
- ≤ 2 chemotherapy regimens for metastatic disease
- Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrolment.
- CNS metastasis is permitted if asymptomatic and not requiring treatment with steroids and is documented to be non-progressing at study entry
- Presence of measurable or evaluable disease by RECIST 1.1 criteria
- Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3, platelet ≥100,000/mm3, hemoglobin ≥ 10g/mm3
- Adequate hepatic function: total bilirubin ≤ 1.5 x upper normal limit (UNL), AST/ALT ≤2.5 x UNL or ≤5 x UNL if presented with hepatic metastasis
- Fasting serum cholesterol ≤ 300mg/dl and fasting triglycerides ≤ 2.5 x UNL
- Adequate renal function: Serum creatinine ≤1.5mg/dL
- Patients should sign a written informed consent before study entry
- Patients with positive HBV-DNA of HBsAg at screening must initiate prophylaxis with appropriate antiviral medication at least one week prior to treatment start
Exclusion Criteria:
- Known active CNS metastasis
- Patients who received prior therapy with gemcitabine
- Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites).
- Patients with more than 3 prior chemotherapy lines for treating metastatic breast cancer.
- Patients who received prior therapy with mTOR inhibitor or PI3K inhibitor
- Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin).
- Radiotherapy within four weeks prior to enrolment, except radiotherapy to the bone for analgesic purpose or for lytic lesions at risk of fracture. Patients must have recovered from radiotherapy toxicities prior to enrolment.
- Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- Active ulceration of upper gastrointestinal tract
- Other concurrent severe and/or uncontrolled conditions (e.g. uncontrolled diabetes mellitus, active untreated or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol.
- Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
- Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A at enrolment (rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir, telithromycin) continuously for at least 7 days during any time period in the last 2 weeks prior to enrolment
- Known hypersensitivity to protocol treatment
- Pregnant or breast feeding
- Peripheral neuropathy ≥ grade 2 (NCI CTCAE version 4.0) at randomization
- Patients unwilling to or unable to comply with the protocol
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:RAD001
gemcitabine 800mg/m2, D1 and D8 iv.
every 3 weeks.
cisplatin 30mg/m2, D1 and D8 iv.
every 3 weeks.
RAD001 5mg QD. po.
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Afinitor 5mg qd. po.
其他名称:
gemcitabine 800mg/m2 iv.
D1 and D8 every 3 weeks
cisplatin 30mg/m2 iv.
D1 and D8 every 3 weeks
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
The recommended dose of the combination of gemcitabine, cisplatin and RAD001 (everolimus) in patients with metastatic triple-negative breast cancer
大体时间:up to 1 year
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phase IB part
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up to 1 year
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Efficacy of gemcitabine and cisplatin with or without RAD001 in patients with metastatic triple-negative breast cancer by evaluating progression free survival (PFS)
大体时间:up to 5 years
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phase II part
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up to 5 years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gemcitabine/cisplatin/RAD001
大体时间:up to 1 year
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phase Ib part
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up to 1 year
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number of patients with adverse events as a measure of safety and tolerability
大体时间:up to 5 years
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phase Ib and phase II
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up to 5 years
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objective response rate
大体时间:up to 1 year
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phase Ib and phase II
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up to 1 year
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Overall survival (OS)
大体时间:up to 5 years
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phase Ib and phase II
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up to 5 years
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check biomarkers associated with the response of RAD001: angiogenesis, metabolism, immune cells profiles
大体时间:up to 5 years
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phaseIb and phaseII
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up to 5 years
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合作者和调查者
调查人员
- 首席研究员:In Hae Park, Doctor、National Cancer Center, Korea
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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