A Phase I Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib (BSI-201) in Multiple Non Operable Brain Metastases
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 4
- 主要终点
- To determine the Maximum Tolerated Dose (MTD)
研究概览
简要总结
Recent pre-clinical and clinical data have indicated that BSI-201 does not possess characteristics typical of the PARP inhibitor class. Based on the results from in vitro and in vivo studies, this trial aims to evaluate the combination of BSI-201 concomitantly with radiotherapy in patients who present with multiple non operable brain metastases. As radiotherapy is a local treatment targeting only the tumor, and because the molecule BSI-201 has shown no major toxicity against tissues without DNA alterations, the proposed combination is expected to provide tumor-selective therapy and leading to a clinical benefit improvement.
Primary objective is to determine the recommended phase II dose (RP2D) and evaluate acute toxicity (CTC-AE v4.0 grading scale) of concurrent administration of whole brain radiotherapy (WBR) and a small molecule BSI-201 in non operable brain metastases.
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
盲法说明
Concurrent whole brain radiotherapy and iniparib
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
- •Non operable brain metastases from any type of cancer (≥ 2)
- •At least one measured brain target available ≥ 1 cm (T1-weighted sequences with contrast application MRI)
- •No stereotaxie indication
- •Any anterior treatments for systemic disease (any chemotherapy at any line) are accepted but have to be interrupted at least 15 days before and up to 30 days after the present protocol
- •No extra-brain disease or stabilized since at least 1 month
- •Aged ≥ 18 years old
- •KPS > 70 (RPS class I or II)
- •Adequate bone marrow function: WBC ≥ 3.5 x 109/L, ANC ≥ 1.5 x 109/L, Platelets ≥ LLN, Hb > 10g/dL,
- •Adequate renal function: serum creatinine ≤ 1.5 × ULN and blood urea nitrogen ≤ 25 mg/dL
- •Male or female patient using adequate contraceptive method
- •Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to the start of treatment
- •Informed and signed consent
- •Able to be followed according to the terms of the protocol
- •Affiliated to the French National social security
排除标准
- •Anterior treatment for brain metastases (surgery, radiosurgery, stereotaxie)
- •Leptomeningeal metastases
- •Inclusion in another protocol within 30 days
- •Brain metastases with severe intracranial hypertension clinical signs
- •Other cancer except the known primary tumor or in situ cervix cancer or basocellular carcinoma
研究组 & 干预措施
Concurrent whole brain radiotherapy and iniparib
干预措施: Radiation combined with iniparib (BSI-201) (Radiation)
结局指标
主要结局
To determine the Maximum Tolerated Dose (MTD)
时间窗: Until 12 week follow-up
The MTD is defined as the dose level at which the Dose Limiting Toxicity (DLT) is observed in more than 20% of patients. The DLT is defined as: Any treatment-related toxicity CTC v4.0 ≥ grade 3(CTC-AE v4.0 grading scale)
次要结局
- Rate of adverse events(Until 6 month follow-up)
- Quality of life(At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6)
- Cognitive functions(At baseline, Week 1, Week 4, Week 6, Week 12 and Month 6)
- Objective response rate(At 6 and 12 weeks after the end of radiotherapy)
- Time to local progression(6 months)
- Local progression-free survival(6 months)