A Phase II Study of Bevacizumab and Erlotinib in Subjects With Advanced Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) or Sporadic Papillary Renal Cell Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- Overall Response Rate
研究概览
简要总结
Background:
- At the present time, there are no drugs that have been proven to work in patients with papillary kidney cancer that has spread (metastasized) beyond the kidneys. Researchers are interested in determining whether the combination of the drugs bevacizumab and erlotinib can be used to treat metastatic papillary kidney cancer.
- Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is an inherited type of papillary kidney cancer (it runs in families). Papillary kidney cancer can also occur sporadically, or without a family connection. More research is needed to determine whether treatments for papillary kidney cancer, such as bevacizumab and erlotinib, work in inherited or sporadic types of kidney cancer, and if so, whether there are any differences.
Objectives:
-To determine the effectiveness of the combination of bevacizumab and erlotinib as a treatment for patients with (1) metastatic HLRCC kidney cancer and (2) metastatic kidney cancer not associated with HLRCC (or sporadic papillary RCC).
Eligibility:
- Individuals 18 years of age or older who have been diagnosed with papillary kidney cancer that has spread beyond the kidneys.
- Participants may have either HLRCC or sporadic papillary kidney cancer.
Design:
- Participants will be screened with a full medical history, physical examination, blood and urine tests, and computed tomography (CT) and other scans to evaluate tumor size and treatment options.
- Participants will receive 28-day treatment cycles of bevacizumab (given intravenously every 2 weeks) and erlotinib (a tablet taken by mouth daily).
- Every cycle, participants will return for regular blood and urine tests. Every other cycle, participants will have imaging scans to assess tumor size and response to treatment. Female participants who have uterine fibroid tumors related to their kidney cancer may have additional scans to assess tumor size and response to treatment.
- Participants will continue to receive treatment on the study until their tumors grow or spread to new areas (disease progression), intolerable side effects develop, a better treatment option becomes available, the study closes, it is unsafe to continue treatment, or the participant decides not to remain in the study.
详细描述
Background
- Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a familial cancer syndrome characterized by a propensity for developing renal cancer, and uterine and cutaneous leiomyomas. The kidney cancer associated with HLRCC is clinically aggressive and is characterized by unique histopathologic features that are sometimes described as type 2 papillary RCC.
- Germline mutations in the fumarate hydratase (FH) gene are the genetic hallmark of HLRCC. Mutational inactivation of FH has been shown to result in Von Hippel-Lindau (VHL)-independent upregulation of hypoxia inducible factor (HIF) and its downstream transcriptional targets.
- The recognition that HIF upregulation may play an important role in the formation and propagation of renal cancer associated with HLRCC suggests that interventions directed against components of this pathway, such as vascular endothelial growth factor (VEGF) and transforming growth factor-alpha/epidermal growth factor receptor (EGFR), may be of benefit in this patient population.
- We propose to test the hypothesis that dual VEGF/EGFR blockade with bevacizumab/erlotinib is likely to be clinically active in patients with HLRCC associated RCC as well as those with sporadic papillary sporadic RCC.
Objective
Primary Objective
-To determine the overall response rate (Response Evaluation Criteria in Solid Tumors (RECIST) in patients with 1) metastatic RCC associated with HLRCC and 2) metastatic sporadic/non-HLRCC papillary renal cancer treated with a combination of bevacizumab and erlotinib
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1 - Bevacizumab and Erlotinib
All patients will be receiving fixed starting dose of bevacizumab (10 mg/kg intravenous (IV) every 2 weeks) and erlotinib (150 mg/day by mouth (PO)
干预措施: Bevacizumab (Drug)
1 - Bevacizumab and Erlotinib
All patients will be receiving fixed starting dose of bevacizumab (10 mg/kg intravenous (IV) every 2 weeks) and erlotinib (150 mg/day by mouth (PO)
干预措施: Erlotinib (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: Every 8 weeks during the first 32 weeks and every 12 weeks thereafter, a median of 64.3 months
Participants whose tumors regressed (Complete Response (CR) plus Partial Response (PR)) after therapy as measured by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is at least a 30% decrease in the sum of the longest diameters of target lesions. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Data shown with 95% confidence intervals.
次要结局
- Progression-free Survival(Amount of time subject survives without disease progression after treatment; a median of 15 months.)
- Duration of Response(Time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented; a median of 19 months.)
- Overall Survival (OS)(Time from the date of study enrolment until time of death; a median of 29.3 months.)
研究者
Ramaprasad Srinivasan, M.D.
Principal Investigator
National Cancer Institute (NCI)