A Phase 4 interventional study of Endoscopic trans-sphenoidal adenoma resection and Dopamine Agonists in Prolactinoma and Prolactin-Producing Pituitary Tumor, sponsored by Leiden University Medical Center. Recruiting at 3 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-07-20.
Sponsored by Leiden University Medical Center · Phase 4, Interventional, and Treatment
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.
28 studies on the registry are indexed under Prolactinoma; 5 are open to participants now.
This study's planned enrollment of 880 is above the median of 55 across 14 interventional studies indexed under Prolactinoma.
Browse Prolactinoma studies →Leiden University Medical Center is the lead sponsor of 334 studies on the registry; 110 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
One of the following, dividing patients in to our three RCTs:
Exclusion Criteria:
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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Procedure: Endoscopic trans-sphenoidal adenoma resection
Patients in the standard care groups will receive treatment as usual as described by the US Endocrine Society.
Drug: Dopamine Agonists
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.
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.
Also known as: Standard Care
Health-Related Quality of Life
Health-Related Quality of Life is defined as the score on the mental health scale of the Medical Outcomes Study (MOS) Short-Form Health Survey (SF-36), measured at T=12.
Time frame: 12 months after randomization/baseline
Long-term remission
Disease remission is defined as normoprolactinaemia (a prolactin level below the upper limit of normal as defined by the laboratory site where it is measured), in the absence of dopamine agonist treatment for at least 3 months or an actual pregnancy that was established during at least 3 months absence of dopamine agonist treatment, measured at T=36.
Time frame: 36 months after randomization/baseline
Short-term remission
Disease remission as defined under the primary outcome for remission, measured at T=27.
Time frame: 27 months after randomization/baseline
Very long-term remission
Disease remission as defined under the primary outcome for remission, measured at T=60
Time frame: 60 months after randomization/baseline
Biochemical disease control
Biochemical disease control is defined as normoprolactinaemia (a prolactin level below the upper limit of normal as defined by the laboratory site where it is measured), or an actual pregnancy, with or without the use of a dopamine agonist, measured at T=12.
Time frame: 12 months after randomization/baseline
Recurrence rate
Disease recurrence is defined as recurrence of hyperprolactinaemia (a prolactin level \>2 times the upper limit of normal as defined by the laboratory site where it is measured) in the absence of dopamine agonist treatment, after a period of normoprolactinaemia (without dopamine agonist treatment). This is measured only in patients who have achieved disease remission at T=27, and is measured at T=36 and T=60.
Time frame: 36 and 60 months after randomization/baseline
Clinical symptom control
Clinical symptom control is defined as the absence of physical and psychiatric symptoms of prolactinoma.
Time frame: 12, 27, 36 and 60 months after randomization/baseline
Tumor shrinkage on MRI
Tumor growth or shrinkage will be calculated as the percentage difference from baseline in tumor size (defined as the maximal diameter measured in mm) and tumor volume (calculated using Cavalieri's principle: tumor volume = 4/3 × pi (a/2 × b/2 × c/2) where a, b and c represent the diameters (in mm) in the 3 dimensions), measured at T=12 and T=36. It will be considered as a relevant shrinkage if tumor diameter or volume decreases at least 20%.
Time frame: 12 and 36 months after randomization/baseline
Pituitary functioning
The functioning of the pituitary axes other than prolactin (i.e. gonadal, thyroidal, corticoid, growth hormone and ADH axes), measured when indicated upon judgement by the treating physician (e.g. when an axis was deviant at baseline of as part of routine follow up after surgery) at T=12 and T=36. A pituitary axis will be considered normal when the associated measurement is within its normal range specific to the laboratory where it was measured in the absence of supplement treatment.
Time frame: 12 and 36 months after randomization/baseline
Complications
Treatment specific adverse effects: - The occurrence of known complications to surgery (i.e. cerebrospinal fluid leakage, diabetes insipidus, syndrome of inappropriate ADH-secretion, nasal complaints, decreased sense of smell/taste, intradural hemorrhage, meningitis, visual loss or a new pituitary deficit), as documented in patients' medical records by the treating physician, measured at T=12.
Time frame: Baseline and 12 months after randomization/baseline
Side effects
Treatment specific adverse effects: - Occurrence of known side effects to dopamine agonist treatment as documented with the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) and a combined Impulse Control Disorder questionnaire at baseline, T=12, T=27 and T=36.
Time frame: Baseline and 12, 27 and 36 months after randomization/baseline
Health-Related Quality of Life
Described by the scores on all sub-scales of the SF-36, in addition to the primary outcome on health-related quality of life. Measured at baseline, T=12, T=27, T=36 and T=60.
Time frame: Baseline and 12, 27, 36 and 60 months after randomization/baseline
Depression and anxiety scores
Measured with the Hospital Anxiety and Depression Scale (HADS). This questionnaire uses 14 items; seven related to anxiety and seven to depression, to calculate anxiety and depression scores, ranging from 0 to 21.
Time frame: baseline and 12 and 36 months after randomization/baseline
Disease burden
Measured with the Leiden Bother and Needs Questionnaire at baseline, T=12, T=36 and T=60.
Time frame: baseline and 12, 36 and 60 months after randomization/baseline
Healthcare costs
Measured every 6 months until T=36, with the iMTA Medical Consumption Questionnaire.
Time frame: Every 6 months until 36 months after randomization/baseline
Non-healthcare costs
Measured every 6 months until T=36, with the iMTA Productivity Cost Questionnaire.
Time frame: Every 6 months until 36 months after randomization/baseline
Quality-Adjusted Life Years (QALYs)
Measured at 3-6 month intervals, with the EQ-5D-5L.
Time frame: Baseline and 6, 9, 12, 18, 24, 27, 30 and 36 months after randomization/baseline
Plan to share: Undecided
Started Jun 2019 (actual). Primary completion is estimated for Mar 2024, 57 months after the start.
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