A Phase II, Randomized, Clinical Trial Assessing Efficacy And Safety Of Oral Prednisolone vs Intravenous Vincristine In The Treatment Of Infantile
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Response of Hemangioma (IH) to Treatment
研究概览
简要总结
The goal of this study is to determine the safety and efficacy of Prednisolone and Vincristine for treatment of large, complicated infantile hemangiomas. The diagnostic, therapeutic and response criteria experimentally determined in this study will be used as a framework for future infantile hemangioma studies.
详细描述
Infants with large hemangiomas are often treated systemically with oral steroids (Prednisolone) to prevent complications. The best treatment for hemangiomas is not known and there are no medications approved by the FDA for treatment of hemangiomas. Also, the best method to measure the response of hemangioma to treatment is not known. Patients enrolling on this study will be randomly assigned to receive either daily Prednisolone by mouth or weekly Vincristine in a vein. Response to treatment will be monitored by clinical exams every two weeks and by an MRI at study entry and six and twelve weeks later. Patients with evidence of progressive disease (larger hemangiomas) on the week 6 MRI will be switched to the other drug to complete a total of 12 weeks of therapy. Side effects of each medication will be monitored closely determined from histories, physical exams, blood tests and other studies as necessary. Participation in this study will last up to 12 weeks and follow up for protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 6 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children age 0-6 months old.
- •Infants with infantile hemangiomas with complications that require systemic therapy to control their growth. To be eligible for enrollment infants must have clear indications for systemic treatment.
- •Clinical diagnosis of infantile hemangioma confirmed by tissue biopsy positive for GLUT-1 Immunohistochemical staining. If the risk of bleeding or permanent disfigurement from biopsy is believed to be too great then clinical and radiological characteristics may be used to establish the diagnosis after discussion with the study PI. Patients with GLUT-1 negative vascular tumors such as Kaposiform hemangioendothelioma, tufted angioma, and angiosarcoma are not eligible.
- •Hemangiomas must be greater than or equal to 50 cm2 clinically measured by taking the product of the two largest perpendicular diameters and have one of the following complications: ulceration, impairment of vision, impairment of hearing, obstruction of the airway, high output cardiac failure, bleeding, abdominal distention and/or compartment syndrome, compression of the spinal cord, or high risk of permanent disfigurement.
- •Adequate liver function defined as:
- •Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and
- •SGPT(serum glutamate pyruvate transaminase) (ALT) < 2.5 x upper limit of normal (ULN) for age.
- •Patients who have received topical or intralesional corticosteroids are eligible to be enrolled. A washout of one week is required prior to study enrollment. Patients who have undergone surgical resection are eligible if they meet all inclusion criteria after surgery.
- •All patients' parents or legal guardians must sign a written informed consent. All institutional and FDA requirements for human studies must be met.
排除标准
- •Children greater then 6 months old.
- •Contraindications to Vincristine: previously diagnosed neuropathy including sensory neuropathy type 1, Charcot- Marie-Tooth or childhood poliomyelitis.
- •Hemangioma involving the central nervous system (CNS) as Vincristine has poor CNS penetration.
- •Infants who have received prior systemic therapy with corticosteroids (oral or intravenous), interferon or Vincristine are not eligible for enrollment.
- •Patients receiving Vincristine who concomitantly require oral steroids for treatment of non-hemangioma indications such as asthma or atopic dermatitis will be removed from study.
- •A life-threatening intercurrent infection.
- •Infants with an underlying illness that would require use of general anesthesia (as opposed to sedation) for the MRI.
研究组 & 干预措施
1
Vincristine is a drug that has been used to treat cancers in children (including infants). It has been effective in treating a small number of infants with hemangiomas, most of whom failed previous therapies including steroids. Vincristine must be administered into a vein. Given the encouraging response data and documented safety record, Vincristine is a good choice for a clinical trial treating infants with complicated hemangiomas.
干预措施: Vincristine (Drug)
2
The standard treatment for hemangioma at most centers is oral steroids (Prednisolone). Prednisolone has been used to stop the growth of infantile hemangiomas that are life threatening, that could harm important functions, or are likely to result in severe disfigurement (scarring) without treatment.
干预措施: Prednisone (Drug)
结局指标
主要结局
Response of Hemangioma (IH) to Treatment
时间窗: 6 weeks
Response of IH not confined to the dermis will be coded using the following criteria: Progressive disease: \>40% increase in volume by MRI, Partial response: \>65% reduction in volume by MRI, Complete response: no visual or radiographic evidence of disease, Stable disease: none of the above or \<40% increase or \<65% decrease in volume by MRI. Response of superficial IH will be coded using the following criteria (based on RECIST): Progressive disease: \>30% increase in IH size, Partial response: \>30% reduction in size, Complete response: no evidence of disease, Stable disease: none of the above. Our first 3 patients showed limits to using MRI volume to measure IH size/response to therapy. Unlike other solid tumors, the superficial distribution of some IH made getting volume by MRI difficult, resulting in smaller tumor estimation compared to clinical assessment. Based on these observations, we amended the protocol to report response based on RECIST criteria instead of change in IH volume.
次要结局
- Toxicity to Medications(Initial visit, 2, 4, 6, 10 and 12 weeks of therapy)
研究者
Beth Drolet
Professor of Dermatology
Medical College of Wisconsin