Neoplasms

Nervous System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Prolactinoma

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pituitary Diseases

Pituitary Neoplasms

Endocrine Gland Neoplasms

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

All Drugs and Chemicals

Cardiotonic Agents

Hormones

Dopamine

Dopamine Agonists

Subjects are treated with CAB tablets 2mg/week or BC tablets 7.5mg/day.The pituitary hormone levels, tumor volume,visual acuity and visual field scale will be measured every 3 months.MRI showed that the tumors shrunk significantly.

Subjects are treated with CAB tablets 2mg/week or BC tablets 7.5mg/day.The pituitary hormone levels, tumor volume, visual acuity and visual field scale will be measured every 3 months. The CAB or BC fail to decrease prolactinoma size.

The medication will be stopped if failure to decrease prolactinoma size and the subjects will be advised to endoscopic transphenoidal pituitary surgery .

Surgery

The medication will continue if DA causes tumors to shrink.

Drug treatment

Weiting Gu, MD

Zhebao Wu, Medical PhD

To study the in vivo expression of dopamine D2 receptors in prolactinoma and the predictive role of dopamine D2 receptors PET-MR imaging in the therapeutic effect of dopamine agonists.

The dopamine agonist(DA),such as cabergoline(CAB) and bromocriptine(BC), has been used widely in the treatment of prolactinomas, but its clinical use is hampered by intolerance and/or resistant in some patients. It had been showed that DA inhibit prolactin secretion by binding to and activating dopamine D2 receptors.PET-MR combined MR images with PET function images is substantial to evaluate the expression of dopamine D2 receptors.The aim is to study the in vivo expression of dopamine D2 receptors in prolactinoma and the predictive role of dopamine D2 receptors PET-MR imaging in the therapeutic effect of DA.

Dopamine D2 Receptors(D2R) Imaging in Prolactinomas

The Predictive Value of Positron Emission Tomography-Magnetic Resonance (PET-MR) Mediated Dopamine D2 Receptors Imaging in the Drug Therapy of of Prolactinomas.

The individual patient Data would not be shared to the third facility, but the sponsor hasn't decided whether to share the individual patient date to the other related studies hold by himself in the future.

Record the result of PRL on every 3 month follow-up visit

Record the tumor volume from enhanced pituitary MRI on every 3 month follow-up visits

Record the Visual field scale on every 3 month follow-up visit, 0 = normal, no vision loss; 1 = one quadrant vision loss; 2 = two quadrants of vision loss; 3 = three quadrants of vision loss; 4 = four quadrants of vision loss but retain a central tubular vision; 5 = blind

Record the Visual acuity on every 3 month follow-up visit.

Xinqiao Hospital of Chongqing

First Hospital of China Medical University

Beijing Tiantan Hospital

First Affiliated Hospital of Wenzhou Medical University

First Affiliated Hospital of Fujian Medical University

Peking Union Medical College Hospital

Huashan Hospital

Chinese PLA General Hospital

Zhebao Wu

Principal Investigator

Behaviors and Mental Disorders

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Quality of Life

Anti-Dyskinesia Agents

Cabergoline

Bromocriptine

Quinagolide

Sympathomimetics

Dopamine Agents

Neurotransmitter Agents

Protective Agents

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.

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

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.

Endoscopic trans-sphenoidal adenoma resection

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.

Ingrid M Zandbergen, MD

Coordinating invesitgator

Local principal investigator

Coordinating investigator

Ingrid M Zandbergen

Nienke R Biermasz, MD, prof.

Wouter R van Furth, MD, PhD

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.

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.

PRolaCT - Three Prolactinoma RCTs

PRolaCT - Three Multicenter Prolactinoma Randomized Clinical Trials

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.

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.

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

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

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.

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.

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

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%.

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.

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.

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.

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

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

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

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

Leiden University Medical Center

Coordinating Investigator

Subjects who show high expression of dopamine D2 receptors in PET-MR imaging.

Subjects who show low expression of dopamine D2 receptors in PET-MR imaging.

Subjects who show high expression of dopamine D2 receptors in PET-MR imaging will be treated with Cabergoline(CAB) tablets 2mg/week or bromocriptine(BC) tablets 7.5mg/ day.The pituitary hormone levels, tumor volume, visual acuity and visual field scale will be measured every 3 months. The medication will be stopped if failure to decrease tumor size and the subjects will be advised to surgical therapy.

Subjects who show low expression of dopamine D2 receptors in PET-MR imaging will be treated with endoscopic transphenoidal pituitary surgery .

To study the in vivo expression of dopamine D2 receptors in nonfunctioning pituitary adenoma and the predictive role of dopamine dopamine D2 receptors PET-MR imaging in the therapeutic effect of dopamine agonists（DA）.

Dopamine agonists are the first line therapy for prolactinoma,which are also effective in some cases of other subtypes of pituitary tumors. It had been showed that dopamine agonists inhibit prolactin secretion by binding to and activating dopamine D2 receptors. PET-MR combined MR images with PET function images is substantial to evaluate the expression of dopamine D2 receptors.The aim is to study the in vivo expression of dopamine D2 receptors in prolactinoma and the predictive role of dopamine D2 receptors PET-MR imaging in the therapeutic effect of dopamine agonists.

Dopamine D2 Receptors(D2R) Imaging in Nonfunctioning Pituitary Adenoma(NFPA)

The Predictive Value of Positron Emission Tomography-Magnetic Resonance (PET-MR) Mediated Dopamine D2 Receptors Imaging in the Drug Therapy of Nonfunctioning Pituitary Adenoma

Change from baseline on tumor volume measured by enhanced pituitary Magnetic Resonance Imaging（MRI）.

Record the tumor volume from enhanced pituitary MRI on every 3 month follow-up visit.

2.Record the Visual field scale on every 3 month follow-up visit, 0 = normal, no vision loss; 1 = one quadrant vision loss; 2 = two quadrants of vision loss; 3 = three quadrants of vision loss; 4 = four quadrants of vision loss but retain a central tubular vision; 5 = blind

Withdrawal observation after reaching the withdrawal standard

Continue treatment obsevation after reaching the withdrawal standard

The purpose of this study is to observe whether dopamine agonists can be safely withdrawn after the tumor volume and prolactin level of invasive prolactinomas involving the cavernous sinus have been effectively controlled through pharmacological treatment.

For giant or large invasive prolactinomas involving the cavernous sinus, whether the drug can be safely withdrawn after the tumor volume and prolactin(PRL) level have been effectively controlled through pharmacological treatment still remains unknown. The study objects are patients with invasive prolactinomas involving the cavernous sinus, which were invaded the cavernous sinus to an extent corresponding to Grade III or IV, according to the classification scheme of Knosp and colleagues, who had undergone pharmacological treatment including bromocriptine or cabergoline. Observation will be started after drug withdrawal criteria are reached (PRL remains normal level for no less than two years; tumor volume has shrank more than 50%, and the distance is more than 5mm between tumor and optical nerve),the patients are randomized to withdrawal group or continue treatment group.Observational items include changes of PRL level, tumor volume as well as vision acuity and visual fields. If elevated PRL or tumor relapse is observed, pharmacological treatment will be restarted.

Whole blood; urine; tumor specimens (if possible)

Dopamine Agonists Withdrawal Study of Invasive Prolactinomas Involving the Cavernous Sinus

Record the Visual acuity on every 3 month follow-up visit

Chief Physician

Pasireotide

Hormone Antagonists

All patients will initiate open-label treatment with pasireotide LAR on week 1 in the outpatient setting. Pasireotide will be initiated at 40 mg IM one time dose and if tolerated dose will be increased to 60 mg IM every 4 weeks +/-7 days. Administration of pasireotide will align with package inset. Patients must return to the study center every 28 days (+/- 7 days) to receive study medication and for evaluation.

Pasireotide will be initiated at 40 mg IM one time dose and if tolerated dose will be increased to 60 mg IM every 4 weeks +/-7 days.

Baseline assessment will be conducted within 30 days of starting treatment, week 12, 24 and week 28.

SF-36 and HADS

Eliza Geer, MD

Andrew Lin, MD

The researchers are doing this study to find out whether pasireotide is an effective treatment for people with prolactinoma who cannot receive dopamine agonist therapy. Another purpose of this study is to find out whether pasireotide is a safe treatment for people with prolactinoma.

This is an open label single-center pilot study.

A Study of Pasireotide in People With Prolactinoma

Pasireotide Treatment for Patients With Prolactinomas Who Need Treatment Beyond Dopamine Agonist Therapy

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

response rate as defined by a normal serum prolactin concentration (\<18.0 ng/ml for a male and \< 29.0 ng/ml for a female

RECIST criteria, V1.1 (30% decrease in longest tumor diameter)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dopamine D2 Receptors(D2R) Imaging in Prolactinomas	NCT03717454	Prolactinoma	Surgery Drug treatment	18 Years - 65 Years	Ruijin Hospital
PRolaCT - Three Prolactinoma RCTs	NCT04107480	Prolactinoma Prolactin-Produ...	Endoscopic tran... Dopamine Agonis...	18 Years -	Leiden University Medical Center
PRolaCT - Three Prolactinoma RCTs	NCT04107480	Prolactinoma Prolactin-Produ...	Endoscopic tran... Dopamine Agonis...	18 Years -	Leiden University Medical Center
Dopamine D2 Receptors(D2R) Imaging in Nonfunctioning Pituitary Adenoma(NFPA)	NCT03714763	Pituitary Adeno...	Drug treatment Surgery	18 Years - 65 Years	Ruijin Hospital
Dopamine Agonists Withdrawal Study of Invasive Prolactinomas Involving the Cavernous Sinus	NCT02536261	Invasive Prolac...		15 Years - 70 Years	Ruijin Hospital
Dopamine D2 Receptors(D2R) Imaging in Prolactinomas	NCT03717454	Prolactinoma	Surgery Drug treatment	18 Years - 65 Years	Ruijin Hospital
A Study of Pasireotide in People With Prolactinoma	NCT06295952	Prolactin-Produ...	Pasireotide SF-36 and HADS	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for dopamine agonist