Safety and Potency of a High Cabergoline Dosage in Microprolactinomas
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 16
- 主要终点
- Remission
研究概览
简要总结
This will be a multicenter, prospective, randomized, open-label trial with women harboring microprolactinomas and treatment naïve. The sample will be added consecutively and randomized into 2 unblinded groups: the high dosage group will receive a high cabergoline (CAB) dose for a period of ~6 months vs the standard dosage group, which will use the lowest needed dose of CAB to achieve normoprolactinemia for 2 years. The primary outcome will be remission rate.
详细描述
Prolactinoma is the most common subtype of pituitary adenoma, and dopamine agonists are the gold standard for treatment, primarily CAB. The SPARAGMOS trial will be an interventional, randomized, open-label, multicenter study utilizing a high dose of CAB for ~6 months to suppress prolactin levels, with the hypothetical goal of achieving greater tumor apoptosis and remission rates. The control group will receive CAB for two years at the lowest dose necessary to achieve normoprolactinemia, as per current guidelines. Of note, for both groups, the final cumulative dose will be similar. The findings from this trial have the potential to inform and redefine future therapeutic strategies for microprolactinoma.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •1. Willing and able to provide written informed consent prior to any study-related procedures
- •2. Adults >18 years old
- •3. Pre-menopausal women
- •4. Presence of signs and symptoms matching prolactinoma
- •5. Hyperprolactinemia, defined as a prolactin (PRL) level ≥2 times the local laboratory maximum level of normality, present at the time of enrolment
- •6. Presence of an identifiable pituitary mass on MRI with a maximum diameter of less than 1cm, independently of Knosp/invasiveness of the cavernous sinus
- •7. Treatment naïve
- •8. Females who engage in heterosexual intercourse must agree to use either a highly effective or a clinically acceptable method of contraception from the beginning of screening to the last study visit, which will include:
- •Hysterectomy or bilateral salpingectomy
- •Bilateral tubal occlusion or ligation
- •Vasectomized partner
- •Intrauterine device (copper or hormonal)
- •Progestogen-only contraception (oral, injectable or implantable)
- •Male or female condom with or without spermicide
- •Sexual abstinence (only when it is the usual and preferred lifestyle of the subject)
排除标准
- •1. History of primary hyperparathyroidism
- •2. Use of combined hormonal contraceptive within the past 4 weeks
- •3. Pregnancy or current pregnancy desire
- •4. Prolactinoma associated with a known genetic syndrome
- •5. Familial history of pituitary adenoma
- •6. Renal failure (estimated glomerular filtration rate <30 mL/min /1.73m2)
- •7. IGF-1 level above the age-adjusted normal range of the local laboratory (IGF 1 >1x ULNR)
- •8. Idiopathic hyperprolactinemia (normal MRI) or presence of macroprolactinemia
- •9. Concomitant mental condition rendering her unable to understand the nature, scope, and possible consequences of the study, and/or decompensated psychiatric disease (i.e. gambling or severe obsessive-compulsive disorder), as judged by the Investigator
- •10. Chronic use of drugs related to hyperprolactinemia (such as metoclopramide, methyldopa, ranitidine, and opioid-related analgesics)
- •11. Resistant prolactinoma, defined as non-normalization of PRL levels with 2mg/w of CAB
- •12. Patients in the high dosage group who did not use 3.5mg/w of CAB for an entire 6 months (due to intolerance or non-compliance) or failed to achieve the target dose for any other reason
- •13. Active malignant disease within the last 5 years, except basal and squamous cell carcinoma of the skin with complete local excision
- •14. Any decompensated chronic condition (i.e. heart failure NYHA 3-4, diabetes with HbA1c >8.5%, hypothyroidism with TSH >10 mIU/L) that, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes
- •15. Male sex
- •16. Cushing stigmas (moon face, muscle weakness, red striation) or suspicious
- •17. Prior radiotherapy of the pituitary gland area for any reason
- •18. Additional pituitary tumor-directed therapy, including temozolomide, everolimus, lapatinib, or cytotoxic chemotherapy
- •19. Hepatopathy with AST/TGO or ALT/TGP >3x the upper limit of normality
研究组 & 干预措施
HIGH CAB dose
干预措施: Cabergoline (Drug)
Conventional therapy
干预措施: Cabergoline (Drug)
结局指标
主要结局
Remission
时间窗: 3, 6 and 12 months after treatment
Compare laboratory and clinical recurrence of hyperPRL at 3, 6 and 12 months after CAB treatment in the high dosage group vs the standard dosage group (conventional treatment). Laboratory recurrence will be characterized after withdrawal from CAB treatment by the presence of PRL levels above 2x the normal upper limit of reference, after a previous period where PRL levels were within the normal range. At least two separate serum samples are needed to confirm recurrence. The time between samples will be more than a week to ensure sustained elevation. Clinical recurrence will be defined as the recrudescence of symptomatic hyperPRL.
次要结局
未报告次要终点
研究者
Andrea Glezer
MD, PhD
University of Sao Paulo General Hospital