PRolaCT - Three Prolactinoma RCTs

Leiden University Medical Center (LUMC)

Status and phase: Enrolling; Phase 4

Conditions: Prolactinoma; Prolactin-Producing Pituitary Tumor

Treatments: Procedure: Endoscopic trans-sphenoidal adenoma resection; Drug: Dopamine Agonists

Study type: Interventional

Funder types: Other

Identifiers

NCT04107480

NL63919.058.18 (Registry Identifier)

PRolaCT

843002806 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 880 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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880 participants in 2 patient groups

Intervention

Experimental group

Description:

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.

Treatment:

Procedure: Endoscopic trans-sphenoidal adenoma resection

Standard care

Active Comparator group

Description:

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

Treatment:

Drug: Dopamine Agonists