NAPAGE: NAb-PAclitaxel and GEmcitabine in Advanced Soft Tissue Sarcoma. A Multicenter Open-label Single Arm Phase Ib/IIa Trial
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 39
- 试验地点
- 8
- 主要终点
- Phase I: Dose-limiting toxicity (DLT)
研究概览
简要总结
A clinical trial with biweekly regimen of gemcitabine and nab-paclitaxel for Soft tissue sarcomas (STSs).
A Promising antitumor activity in patients with metastatic STS has been reported with gemcitabine alone or in combination with taxanes including docetaxel and paclitaxel in pre-treated patients.
Nab-paclitaxel is a 130-nm albumin-bound formulation of paclitaxel particles (Celgene, Summit, NJ) which was designed to eliminate the toxicities associated with Cremophor®-EL. Nab-paclitaxel at equal dose of paclitaxel showed increased antitumor activity, enhanced endothelial cell transport and 33% higher intra-tumor paclitaxel concentration in preclinical models of solid tumor xenografts promising an advantageous pharmacokinetic profile In sarcoma, nab-paclitaxel demonstrated preclinical anti-tumor activity in rhabdomyosarcoma xenograft model. Local relapsed tumors following paclitaxel treatment proved to be paclitaxel-resistant but remained responsive to nab-paclitaxel.
These findings provide the rationale for further evaluation of nab-paclitaxel in combination with gemcitabine for soft tissue sarcoma treatment.
详细描述
Soft tissue sarcomas (STSs) account for 1% of all human cancers and consist of at least 50 different histological subtypes which have different clinical behavior and response to chemotherapy. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis with a median OS between 12 and 15 months.
Palliative chemotherapy is the mainstay of treatment in the metastatic setting, although in a small subset with limited metastases local treatment may be curative. First-line treatment for advanced soft-tissue sarcoma includes doxorubicin hydrochloride, alone or in combination with other chemotherapy agents (e.g., ifosfamide), or olaratumab. Beyond first line several agents have shown activity, including gemcitabine/docetaxel, trabectedin and pazopanib, though no standard regimen has been established.
Promising antitumor activity in patients with metastatic STS has been reported with gemcitabine alone or in combination with taxanes including docetaxel and paclitaxel in pre-treated patients.
Nab-paclitaxel is a 130-nm albumin-bound formulation of paclitaxel particles (Abraxane®, Celgene, Summit, NJ) which was designed to eliminate the toxicities associated with Cremophor EL®. Nab-paclitaxel at equal dose of paclitaxel showed increased antitumor activity, enhanced endothelial cell transport and 33% higher intra-tumor paclitaxel concentration in preclinical models of solid tumor xenografts promising an advantageous pharmacokinetic profile In sarcoma, nab-paclitaxel demonstrated preclinical antitumor activity in rhabdomyosarcoma xenograft model. Local relapsed tumors following paclitaxel treatment proved to be paclitaxel-resistant but remained responsive to nab-paclitaxel.
These findings provide the rationale for further evaluation of nab-paclitaxel in combination with gemcitabine for soft tissue sarcoma treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed minimum grade 2, locally advanced or metastatic STS refractory to chemotherapy and not suitable for local treatment.
- •Minimum one line and maximum 2 lines of previous chemotherapy for advanced/metastatic STS
- •Measurable disease according to RECIST v1.1
- •Age ≥ 18 years
- •WHO performance status 0-2
- •Adequate hematological, hepatic and renal function
- •Negative pregnancy test
- •Effective method of birth control
- •Peripheral neuropathy at enrolment must be ≤ grade 1
排除标准
- •Uncontrolled CNS metastases
- •Previous or concomitant malignancy diagnosed within 3 years
- •More than 2 lines of previous systemic treatment for STS
- •Previous sarcoma treatment with gemcitabine and/or nab-paclitaxel or other taxanes
- •Radiotherapy within 4 weeks prior to registration
- •Concurrent or recent treatment with any other experimental drug
- •Concomitant use of other anti-cancer drugs
- •Severe or uncontrolled cardiovascular disease
- •History of cerebrovascular accident or intracranial hemorrhage within 2 months prior to registration
- •Evidence of active, noninfectious pneumonitis or history of interstitial lung disease
- •Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B Virus infection or any uncontrolled active systemic infection
- •Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information
- •Known hypersensitivity to the trial drug(s)
研究组 & 干预措施
nab-paclitaxel and gemcitabine
Treatment consists of the combination treatment of nab-paclitaxel and gemcitabine, which is given every 2 weeks during 28-day cycle intervals until disease progression.
干预措施: Nab-Paclitaxel (Drug)
nab-paclitaxel and gemcitabine
Treatment consists of the combination treatment of nab-paclitaxel and gemcitabine, which is given every 2 weeks during 28-day cycle intervals until disease progression.
干预措施: gemcitabine (Drug)
结局指标
主要结局
Phase I: Dose-limiting toxicity (DLT)
时间窗: during the first cycle of treatment (28 days)
DLT is defined as any of the following adverse events (AEs) occurring during the first cycle of treatment and regarded by the investigators and/or the Sponsor to be related to nab-paclitaxel and/or gemcitabine (AEs not related to the IMPs are not regarded as DLT)
Phase II: Progression-free rate (PFR)
时间窗: at 12 weeks after registration
PFR at 12 weeks after registration determined by the percentage of progression-free patients at 12 weeks. Progression is defined as one of the following events (whichever occurs first): * Progressive disease (PD) assessed according to the RECIST v1.1 before week 13 (allowed is a 1 week delay in the tumor assessment at week 12). * Death due to any cause up to week 12. * Start of second line treatment before week 12. * No tumor assessment after week 11 without subsequent treatment which shows stabilization or response.
次要结局
- Phase I: PFR 12 weeks(at 12 weeks after registration)
- Phase I: Best response assessed according to RECIST v1.1(assessed for up to 5 years after patient registration)
- Phase II: Overall Survival (OS)(assessed for up to 5 years after patient registration)
- Phase II: AEs, assessed according to NCI CTCAE v4.03(from registration until 28 days after administration of the last dose of trial treatment)
- Phase II: Nab-paclitaxel related sensory neuropathy assessed by questionnaires(assessed for up to 5 years after patient registration)
- Phase II: Progression-free survival (PFS)(assessed for up to 5 years after patient registration)
- Phase I: Adverse events (AEs), assessed according to NCI CTCAE v4.03(assessed for up to 5 years after patient registration)
- Phase II: Best response assessed according to RECIST v1.1(assessed for up to 5 years after patient registration)
- Phase II: Symptom-related quality of life assessed by questionnaires(assessed for up to 5 years after patient registration)