RecruitingPhase 4NCT04107480

PRolaCT - Three Prolactinoma RCTs

PRolaCT - Three Multicenter Prolactinoma Randomized Clinical Trials

Sponsor

Leiden University Medical Center

Enrollment

880 participants

Start Date

Jun 21, 2019

Study Type

INTERVENTIONAL

Conditions

Prolactinoma Prolactin-Producing Pituitary Tumor

Summary

This study aims to investigate if endoscopic trans-sphenoidal prolactinoma resection as a first line treatment, or as an equally valid second line treatment after a short (4-6 months) or long (\>2 years) period of pretreatment with a dopamine agonist is superior to standard care for several outcome parameters. The main objectives are to investigate this for quality of life and remission rate. The secondary objectives are to investigate this for biochemical disease control, recurrence rates, clinical symptom control, tumor shrinkage on MRI, pituitary functioning, the occurrence of adverse reactions to treatment, disease burden, and cost-effectiveness.

Eligibility

Min Age: 18 Years

Inclusion Criteria10

At least 18 years of age.
A history of signs and symptoms compatible with the diagnosis prolactinoma.
New, recent (PRolaCT-1) or known diagnosis of hyperprolactinaemia, defined as a prolactin level 2 times the local laboratory maximum. At the time of randomization hyperprolactinaemia is still present, or was present \< 12 months before inclusion (PRolaCT-2 and PRolaCT-3).
No clear alternative explanation for hyperprolactinaemia, e.g. medication use.
Presence of a clearly identifiable (persisting) pituitary mass on MRI not invading the cavernous sinus and having an optimal chance to be completely resected (generally adenomas with a maximum diameter nog exceeding 25mm). A representative MRI at the time of randomization is required, this MRI should generally not be older than 12 months in PRolaCT-3 and 2 months in PRolaCT-1 and PRolaCT-2.
Competent and able to fill in questionnaires.
One of the following, dividing patients in to our three RCTs:
PRolaCT-1: no prior treatment for prolactinoma;
PRolaCT-2: treatment with a dopamine agonist for 4-6 months; or
PRolaCT-3: treatment with a dopamine agonist for at least 2 years.

Exclusion Criteria8

Contraindication for one of the treatment modalities, e.g. severe side effect of cabergoline, contraindications to surgery, or a clear indication for surgical resection.
Pregnancy at the time of randomization.
Clinical acromegaly.
Prior pituitary gland surgery or radiotherapy to the pituitary gland area.
Severe renal failure (eGFR \<30 ml/min).
Insufficient understanding of the Dutch or English language.
Other medical conditions that to the opinion of the physician are not compatible with inclusion in a trial.
Patients eligible for participation in one of the RCTs, but do not consent to randomisation or in whom there is a clear patient or physician preference for either DA treatment or surgery, are considered for participation in PRolaCT-O.

Interventions

PROCEDUREEndoscopic trans-sphenoidal adenoma resection

Neurosurgical consultation consists of at least one consult with a neurosurgeon and at least one consult with an endocrinologist with relevant experience. If the multidisciplinary team (MDT) agrees the patient is a good surgical candidate, the patient is asked consent for surgery, as is a custom part of preoperative requirements. When the patient decides not to have the surgery, (s)he will receive standard medical treatment, but will continue study follow up in the intervention group. Surgery only takes place if both the MDT and the patient agree to it and should then be planned within three months after randomization. Surgery is performed by one or two trained neurosurgeons in the hospital where the counseling took place. A standard, semi-protocolled, endoscopic trans-sphenoidal surgical resection of the prolactinoma is performed according to standard practice.

DRUGDopamine Agonists

The treating physician adheres to the treatment protocol in general, but has freedom to choose treatment to his/her ideas how to deliver best care. Current first line treatment consists of a dopamine agonists: cabergoline (currently the most used), bromocriptine or quinagolide. All dopamine agonists are taken orally, and the dosage may be raised based on its effect. It is usually titrated to achieve a normal or suppressed prolactin level and restoration of the gonadal axis. Dopamine agonist treatment is discontinued after 2 years of treatment, unless a normal prolactin level cannot be achieved. The dopamine agonist is restarted when prolactin levels rise after the medication is discontinued. In standard care, surgical treatment is reserved for patients who don't tolerate medication, or whose adenoma fails to show a sufficient response. Patients in the control group with an intolerance for dopamine agonists or an insufficient response may be offered surgery as part of standard care.