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ProlactinomaPhase 4NCT04107480

PRolaCT - Three Prolactinoma RCTs

A Phase 4 study testing Endoscopic trans-sphenoidal adenoma resection and Dopamine Agonists in people with Prolactinoma and Prolactin-Producing Pituitary Tumor, run by Leiden University Medical Center at 3 sites in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Endoscopic trans-sphenoidal adenoma resection and Dopamine Agonists
Could I receive a placebo?
No, everyone receives an active treatment
How many people
880 participants
Where
3 sitesNetherlands
Study dates
21 Jun 2019to 31 Mar 2026
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 10Show fewer
  • 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.

Who cannot join

  • 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 locations and contacts

3 sites in 1 country.

Ingrid M Zandbergen, MD contact

+3171-5296748

i.m.zandbergen@lumc.nl

Coordinating invesitgator contact

+3171-5296748

prolactinoom@lumc.nl

Netherlands3 sites, 3 recruiting

  • Amsterdam University Medical Center, loc. AMC

    Amsterdam-Zuidoost, North Holland, 1105 AZ

    Local principal investigator, +3120-5663542

    Coordinating investigator, +3171-5296748, prolactinoom@lumc.nl

    Not yet recruiting

  • Reinier de Graaf Gasthuis

    Delft, South Holland, 2625 AD

    Local principal investigator, +3115-2604207

    Coordinating investigator, +3171-5296748, prolactinoom@lumc.nl

    Not yet recruiting

  • Leiden University Medical Center

    Leiden, South Holland, 2333 ZA

    Coordinating investigator, +3171 5296748, prolactinoom@lumc.nl

    Ingrid M Zandbergen, i.m.zandbergen@lumc.nl

    Recruiting

Other trials in Netherlands

About this study

Official title: PRolaCT - Three Multicenter Prolactinoma Randomized Clinical Trials

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.

Being tested
Endoscopic trans-sphenoidal adenoma resection, Dopamine Agonists
Keywords
prolactinoma, dopamine agonist, endoscopic trans-sphenoidal adenoma resection, remission rate, health-related quality of life
Medical subject headings
Prolactinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Endoscopic trans-sphenoidal adenoma resectionProcedure or surgery

    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.

  • Dopamine AgonistsDrug

    Also called Standard Care

    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.

Study groups in NCT04107480
Study groupRoleWhat they receive
InterventionExperimentalPatients 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.
Receives: Procedure: Endoscopic trans-sphenoidal adenoma resection
Standard careActive comparatorPatients in the standard care groups will receive treatment as usual as described by the US Endocrine Society.
Receives: Drug: Dopamine Agonists

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 12 months after randomization/baseline

  2. 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.

    Measured: 36 months after randomization/baseline

Secondary outcomes (15)

  1. Short-term remission

    Disease remission as defined under the primary outcome for remission, measured at T=27.

    Measured: 27 months after randomization/baseline

  2. Very long-term remission

    Disease remission as defined under the primary outcome for remission, measured at T=60

    Measured: 60 months after randomization/baseline

  3. 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.

    Measured: 12 months after randomization/baseline

  4. 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.

    Measured: 36 and 60 months after randomization/baseline

  5. Clinical symptom control

    Clinical symptom control is defined as the absence of physical and psychiatric symptoms of prolactinoma.

    Measured: 12, 27, 36 and 60 months after randomization/baseline

  6. 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%.

    Measured: 12 and 36 months after randomization/baseline

  7. 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.

    Measured: 12 and 36 months after randomization/baseline

  8. 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.

    Measured: Baseline and 12 months after randomization/baseline

  9. 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.

    Measured: Baseline and 12, 27 and 36 months after randomization/baseline

  10. 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.

    Measured: Baseline and 12, 27, 36 and 60 months after randomization/baseline

  11. 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.

    Measured: baseline and 12 and 36 months after randomization/baseline

  12. Disease burden

    Measured with the Leiden Bother and Needs Questionnaire at baseline, T=12, T=36 and T=60.

    Measured: baseline and 12, 36 and 60 months after randomization/baseline

  13. Healthcare costs

    Measured every 6 months until T=36, with the iMTA Medical Consumption Questionnaire.

    Measured: Every 6 months until 36 months after randomization/baseline

  14. Non-healthcare costs

    Measured every 6 months until T=36, with the iMTA Productivity Cost Questionnaire.

    Measured: Every 6 months until 36 months after randomization/baseline

  15. Quality-Adjusted Life Years (QALYs)

    Measured at 3-6 month intervals, with the EQ-5D-5L.

    Measured: Baseline and 6, 9, 12, 18, 24, 27, 30 and 36 months after randomization/baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2019
  2. Study start21 Jun 2019
  3. Primary completion31 Mar 2024 (estimated)
  4. Study completion31 Mar 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This partially randomized, preference trial design, comprises three unblinded randomized controlled trials (RCTs) and an observational study arm (PRolaCT-O) that compare neurosurgical counselling and potentially subsequent endoscopic transsphenoidal adenoma resection with current standard care (DA treatment). Patients with a non-invasive prolactinoma of limited size (\<2.5 cm) will be divided over the three RCTs based on duration of pre-treatment with DA: PRolaCT-1: newly diagnosed, treatment naive patients; PRolaCT-2: patients with limited duration of DA treatment (4-6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for \>2 years. PRolaCT-O will include patients who decline randomization or those with a clear treatment preference. After study inclusion and treatment allocation, all study procedures and follow up are equal for the three RCTs and PRolaCT-O and are therefore discussed as one.
Masking
None (open label)
Enrolment
880 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04107480
Sponsor's protocol ID
PRolaCT
Other IDs
843002806, NL63919.058.18
Status last verified
Jul 2020
First submitted
27 Aug 2019
Last updated
20 Jul 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Zandbergen IM, Zamanipoor Najafabadi AH, Pelsma ICM, van den Akker-van Marle ME, Bisschop PHLT, Boogaarts HDJ, van Bon AC, Burhani B, le Cessie S, Dekkers OM, Drent ML, Feelders RA, de Graaf JP, Hoogmoed J, Kapiteijn KK, van der Klauw MM, Nieuwlaat WCM, Pereira AM, Stades AME, van de Ven AC, Wakelkamp IMMJ, van Furth WR, Biermasz NR; Dutch Prolactinoma Study Group. The PRolaCT studies - a study protocol for a combined randomised clinical trial and observational cohort study design in prolactinoma. Trials. 2021 Sep 25;22(1):653. doi: 10.1186/s13063-021-05604-y.

    PubMed 34563236

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Endoscopic trans-sphenoidal adenoma resection and Dopamine Agonists in people with Prolactinoma and Prolactin-Producing Pituitary Tumor, run by Leiden University Medical Center at 3 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 20 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ingrid M Zandbergen, MD (+3171-5296748, i.m.zandbergen@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Health-Related Quality of Life (time frame: 12 months after randomization/baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04107480, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2020.

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PRolaCT - Three Prolactinoma RCTs (NCT04107480) | AzTrials