An Open Label Dose Escalation and Pharmacokinetic Phase I Study With Pazopanib in Combination With Cisplatin (CDDP) Every Three Weeks in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- UNICANCER
- 入组人数
- 35
- 试验地点
- 5
- 主要终点
- Determination of the Optimal Tolerated Regimen (OTR) based on the occurrence of Dose Limiting Toxicities
研究概览
简要总结
The aim of this research is to evaluate the potential interest of an association of Pazopanib, a multi-tyrosine kinase inhibitor, and cisplatin.
As cisplatin has marketing approval for several cancers (ovarian, testicle, bladder, esophagus, endometrium, lung, stomach, head and neck cancer (HNC)), and in order to have a rapid evaluation of this combination, we will evaluate the combination in any patient whose tumors is known to be sensible to cisplatin (except tumors at risk of bleeding).
This study is a classical phase 1 trial of pazopanib and 3-weekly cisplatin association. It will allow for optimal dose selection and pharmacokinetic analysis. It is planed to include around 38 patients, enriching the optimal tolerated regimen (OTR) level only with a cohort of triple negative breast cancer patients. If the association is proven to be feasible, we will then move to a specific phase II study in triple negative breast cancer patients.
详细描述
The main objective of the study is to determine the dose limiting toxicities (DLT) and the optimal tolerated regimen (OTR) which are both safety criteria evaluated upon the NCI CTC-AE system version 4.0.
Efficacy is not the primary objective; however the anti-tumor activity of the pazopanib/cisplatin combination will be carried out by the determination of the objective response rate according to RECIST criteria version 1.1.
The objective response is defined as either a complete response (CR) or partial response (PR), assessed either by CT Scan and/or MRI and/or bone Scan, performed at baseline and every 6 weeks.
This is an open-label, non-randomized, dose escalation and pharmacokinetic, phase I study pazopanib with cisplatin in patients with relapsed or refractory solid tumors (except tumors at risk of bleeding) for whom the selected combined chemotherapy is indicated or is a reasonable option (as per tumor characteristics and previous treatments).
All eligible patients entering the study will receive daily oral pazopanib, supplied as 200 mg aqueous film-coated tablets and intravenous cisplatin every three weeks. Doses of both compounds will be adjusted according to the reached dose level.
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
- •Documented metastatic solid malignancies for patients who are candidate to receive a cisplatin based regimen.
- •During the dose seeking procedure : ALL solid tumors
- •During the Optimal Tolerated Regimen validation procedure : ONLY HER2-RH- breast cancer
- •Measurable or evaluable disease
- •WHO performance status ≤ 1
- •Negative dipstick proteinuria test or if positive proteinuria <1g/24h. If proteinuria appears ≥ 2+ on routine dipstick testing, patients must undergo a 24H -urine collection and demonstrate proteinuria < 1g/24H
- •Corrected QT interval (QTc) ≤ 480 msecs using Bazett's formula
排除标准
- •Prior treatment with cisplatin reaching a cumulative dose> 300 mg/m2
- •HER2 positive breast cancer
- •Patients at high risk of bleeding
- •Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
- •calcium and magnesium levels inferior to standard levels (measured within 14 days before the first pazopanib dose) and potassium levels inferior to standard levels (measured within 72 hours before the first pazopanib dose)
- •Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study
- •Hearing impairment/tinnitus > or = grade 2
研究组 & 干预措施
Pazopanib and Cisplatin
- Steady state period:Pazopanib will be given 8 days prior to cisplatin
- Then pazopanib will be given 400 mg, 600 mg or 800 mg/day, daily and cisplatin 60, 75 or 100 mg/m2 , day 1 - 3 weekly, depending of the dose level
干预措施: cisplatin (Drug)
Pazopanib and Cisplatin
- Steady state period:Pazopanib will be given 8 days prior to cisplatin
- Then pazopanib will be given 400 mg, 600 mg or 800 mg/day, daily and cisplatin 60, 75 or 100 mg/m2 , day 1 - 3 weekly, depending of the dose level
干预措施: Pazopanib (Drug)
结局指标
主要结局
Determination of the Optimal Tolerated Regimen (OTR) based on the occurrence of Dose Limiting Toxicities
时间窗: cycles 1 and 2
次要结局
- To characterize the pharmacokinetic (PK) profile of the combination pazopanib and cisplatin(Cycles 1 and 2)
- Objective response - Overall Objective response rate - Clinical Benefit Rate(At baseline and every 6 weeks.)