PRolaCT - Three Prolactinoma RCTs - National Pediatric Brain Tumor Foundation

PRolaCT - Three Prolactinoma RCTs

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- 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 Criteria:

- 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04107480
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 4
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Leiden University Medical Center
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Nienke R Biermasz, MD, prof.Wouter R van Furth, MD, PhD
Principal Investigator Affiliation	Endocrinologist LUMCNeurosurgeon LUMC
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Netherlands
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Prolactinoma, Prolactin-Producing Pituitary Tumor

Arms & Interventions

Arms

Experimental: Intervention

Patients in the intervention groups will be referred to one of the participating neurosurgical centers, for surgical consultation. After this consultation, the patient may choose to continue with surgery or not.

Active Comparator: Standard care

Patients in the standard care groups will receive treatment as usual as described by the US Endocrine Society.

Interventions

Procedure: - Endoscopic 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.

Drug: - Dopamine 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.

Contact a Trial Team

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