A Multicenter, Open, Prospective, Observational Study to Investigate the Effect of Lanreotide Autogel 120 mg on Control of GH and IGF-I Excess and Tumor Shrinkage in Newly Diagnosed Patients With Acromegaly
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Control of GH and IGF-I excess and tumor shrinkage
研究概览
简要总结
Recently, a new formulation of lanreotide, lanreotide Autogel (ATG) 60 mg, 90 mg and 120 mg was developed in order to further extend the duration of the release of the active ingredient. The ATG formulation consists of a solution of lanreotide in water with no additional excipients. ATG was found to have linear pharmacokinetics for the 60 to 120 mg doses and provided a prolonged dosing interval and good tolerability (1). In some previous studies, the ATG was demonstrated as effective as the micro-particle lanreotide (2,3) and as octreotide-LAR in patients with acromegaly (4-7).
Data on the efficacy of ATG in newly diagnosed patients with acromegaly are still lacking. Similarly, the prevalence and amount of tumor shrinkage after ATG treatment is unknown. This information is particularly useful in the setting of first-line therapy of acromegaly that is currently becoming a more frequent approach to the disease (8). It is demonstrated that approximately 80% of the patients treated with depot somatostatin analogues as first line have a greater than 20% tumor shrinkage during the first 12 months of treatment (9). A definition of significant tumor shrinkage was provided in 14 studies (including a total number of patients of 424) and the results showed that 36.6% (weighted mean percentage) of patients receiving first-line somatostatin analogues therapy for acromegaly had a significant reduction in tumor size (10). About 50% of the patients were found to have a greater than 50% tumor shrinkage within the first year of treatment (10); in this study we found that percent decrease in IGF-I levels was the major determinant of tumor shrinkage (10).
The current open, prospective study is designed to investigate the prevalence and amount of tumor shrinkage in newly diagnosed patients with acromegaly treated first-line with ATG.
详细描述
This is an open, prospective, observational, clinical study to be performed in two University Hospitals (Naples and Genova, Italy). The primary objective is to evaluate the efficacy of the ATG 120 mg on control of GH and IGF-I excess in acromegaly according with the currently accepted criteria (12) and on tumor shrinkage. The secondary objectives are to assess improvement of clinical symptoms and safety profile. The study population will consist of at least 20 patients, enrolled in the two centers from Jan 1st 2003 to June 30th 2007. Patients give their written informed consent prior to entering into the study. The study was performed according to the principles defined by the declaration The safety population, as defined by the protocol, consists of patients who received at least one study drug dosing.
Hormonal evaluation GH levels are assessed as a mean value of 5 samples at 30-min intervals (starting between 08:00 and 9:00 in the morning) taken at each visit before the injection of ATG. IGF-I levels are assessed as a single sample taken at each visit at the same time as the first GH sample. All hormonal parameters were assessed in a central laboratory (University of Genoa).
Improvement in clinical symptoms is considered on the basis of a semiquantitative scale for asthenia, hyperhidrosis, headache, swelling of extremities, arthralgia, paraesthesia, carpal tunnel syndrome: symptoms were graded as 0 = absent, 1 = mild, 2 = moderate, 3 = severe.
Any adverse event (AE) during the study is monitored and reported by the investigators. Safety, evaluated by local laboratory data, is assessed at inclusion and at the final visit by: hematology: erythrocytes, leukocytes, platelets, haemoglobin, hematocrit; biochemistry: glucose, creatinine, alkaline phosphatase, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), electrolytes (sodium, potassium, calcium, phosphorous) glycosylated haemoglobin, triglycerides, total and high density lipoproteins (HDL) cholesterol, blood amylase, iron, transferrin, prothrombin; glucose and insulin concentrations; hormonal evaluation: thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free triiodothyronine (FT4), follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. Safety related to gallbladder is assessed by ultrasound examination performed at inclusion and at the end of the study.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with active acromegaly [serum GH levels above 2.5 μg/liter and/or above 1 μg/liter after oral glucose tolerance test (OGTT) and abnormal IGF-I values] with a micro- (<10 mm max tumor diameter) or macroadenoma (>10 mm max tumor diameter)
- •Patients never treated before
- •Patients who do not require immediate surgery because of neurological symptoms and/or emergency conditions
- •Patients who signed an informed consent to participate to the study.
排除标准
- •Patients already treated before with surgery or radiotherapy or with medical treatment
- •Patients with mixed GH-PRL adenomas who require combined somatostatin and dopamine treatment
研究组 & 干预措施
A
Newly diagnosed patients with acromegaly
干预措施: Lanreotide-Autogel 120 mg (Drug)
结局指标
主要结局
Control of GH and IGF-I excess and tumor shrinkage
时间窗: 3 and 12 months
次要结局
- Improvement of clinical symptoms and safety profile(3 and 12 months)