PRolaCT - Three Prolactinoma RCTs

NCT04107480 | Recruiting Phase 4 DMC

• 3 other identifiers: PRolaCT843002806NL63919.058.18
• Study Type: interventional
• Target: 880
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Prolactinoma; Prolactin-Producing Pituitary Tumor

Keywords

prolactinoma; dopamine agonist; endoscopic trans-sphenoidal adenoma resection; remission rate; health-related quality of life

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  36 months after randomization/baseline

Secondary Outcomes (15)

• Short-term remission

  27 months after randomization/baseline

• Very long-term remission

  60 months after randomization/baseline

• Biochemical disease control

  12 months after randomization/baseline

• Recurrence rate

  36 and 60 months after randomization/baseline

• Clinical symptom control

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

Study Arms (2)

Intervention

EXPERIMENTAL

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

Standard care

ACTIVE COMPARATOR

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

Drug: Dopamine Agonists

Interventions

Endoscopic trans-sphenoidal adenoma resection PROCEDURE

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.

Intervention

Dopamine Agonists DRUG

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

Standard care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age.
• A history of signs and symptoms compatible with the diagnosis prolactinoma.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (3)

Amsterdam University Medical Center, loc. AMC

Amsterdam-Zuidoost, North Holland, 1105 AZ, Netherlands

NOT YET RECRUITING

Reinier de Graaf Gasthuis

Delft, South Holland, 2625 AD, Netherlands

NOT YET RECRUITING

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 34563236 DERIVED

MeSH Terms

Conditions

Prolactinoma

Interventions

Dopamine Agonists; Standard of Care

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pituitary Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Nienke R Biermasz, MD, prof.

  Endocrinologist LUMC

  PRINCIPAL INVESTIGATOR

• Wouter R van Furth, MD, PhD

  Neurosurgeon LUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ingrid M Zandbergen, MD

CONTACT

+3171-5296748; i.m.zandbergen@lumc.nl

Coordinating invesitgator

CONTACT

+3171-5296748; prolactinoom@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating Investigator

Model Details: 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.

Study Record Dates

• First Submitted: August 27, 2019
• First Posted: September 27, 2019
• Study Start: June 21, 2019
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2026
• Last Updated: July 20, 2020

Record last verified: 2020-07

Locations

NL (3)