A Phase I/II Study of PTK787 in Combination With Trastuzumab in Patients With Newly Diagnosed HER2 Overexpressing Locally Recurrent or Metastatic Breast Cancer: Hoosier Oncology Group Trial BRE04-80
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 7
- 试验地点
- 8
- 主要终点
- Phase I Cohorts:
研究概览
简要总结
HER2 gene amplification increases VEGF production in breast cancers; combined inhibition of HER2 and VEGF enhances response in xenograft models. The upregulation of VEGF in HER2-overexpressing breast cancers may contribute to the aggressive phenotype observed in HER2-positive breast cancer. New therapeutics targeting VEGF and/or its receptors may enhance the efficacy of trastuzumab monotherapy.
This trial will investigate the safety and efficacy of combined HER2 and VEGF inhibition.
详细描述
OUTLINE: This is a multi-center study.
PTK787 daily plus trastuzumab 4 mg/kg IV week 1, followed by 2 mg/kg weekly with disease evaluation every other cycle.
Patients may continue treatment until disease progression or toxicity intervenes.
Performance Status: ECOG 0 or 1
Life Expectancy: Not specified
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologic or cytologic diagnosis of breast cancer with evidence of measurable (1) unresectable, locally recurrent, or (2) metastatic disease. Locally recurrent disease must not be amenable to resection OR radiation with curative intent.
- •Patient's disease may not involve more than 3 metastatic sites. In addition, patient may not be symptomatic from pulmonary metastasis or have liver metastasis involving > 50% of parenchyma.
- •HER2 gene amplification by FISH. HER protein overexpression by immunohistochemistry will not be sufficient for entry.
- •Negative pregnancy test
排除标准
- •No prior cytotoxic chemotherapy or trastuzumab for locally recurrent or metastatic disease.
- •No prior treatment with any VEGF inhibiting agents
- •No history or presence of central nervous system (CNS) disease.
- •No other forms of cancer therapy including radiation, chemotherapy and hormonal therapy within 21 days prior to being registered for protocol therapy.
- •No major surgery within 28 days prior to being registered for protocol therapy.
- •No uncontrolled hypertension (SBP > 170, DBP > 90), history of labile hypertension or history of poor compliance with antihypertensive therapy.
- •No requirement for therapeutic anticoagulation, regular aspirin (> 325 mg/day) or NSAID use.
- •No current breast feeding.
- •No impairment of gastrointestinal (GI) function that may significantly alter the absorption of PTK
- •No evidence of other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator).
研究组 & 干预措施
Single Group Assignment
Trastuzumab + PTK787 for HER2 positive patients
干预措施: PTK787 (Drug)
Single Group Assignment
Trastuzumab + PTK787 for HER2 positive patients
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Phase I Cohorts:
时间窗: 18 months
Phase II Cohorts:
时间窗: 18 months
The primary objective is to ensure the safety and tolerability of the combination of Trastuzumab and PTK787,
时间窗: 18 months
To assess response rate of PTK787 combined with trastuzumab in patients with newly diagnosed HER2 overexpressing
时间窗: 18 months
次要结局
- Phase II Cohorts:(12 months)
- To assess the safety and tolerability of PTK787 combined with trastuzumab(12 months)
- To assess the time to progression and clinical benefit of PTK787 combined with trastuzumab(12 months)
研究者
Kathy Miller, MD
Professor, IU School of Medicine
Hoosier Cancer Research Network