Clinical trial NCT00690898: Lanreotide as Primary Treatment for Acromegalic Patients With Pituitary Gland Macroadenoma
Official title: Phase IIIb, Multicentre, Open-label, Single-arm, Study to Assess the Efficacy and Safety of Lanreotide Autogel 120 mg Administered Every 28 Days as Primary Medical Treatment in Acromegalic Patients With Macroadenoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acromegaly
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2008-06-05
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Acromegaly is a chronic disease caused by excessive secretion of growth hormone (GH) and mainly due to benign tumour localized in the pituitary gland.

The disease develops insidiously, causing a gradual progression of symptoms; consequently most patients are diagnosed in their fourth decade of life.

Administration of somatostatin analogues such as lanreotide have been shown to result in normalisation or the decrease of GH and insulin growth factor (IGF-1) levels and improvement of clinical symptoms in acromegalic patients. The purpose of this study is to evaluate whether lanreotide is also effective on tumour volume reduction (tumour shrinkage) and the benefits of this potential tumour shrinkage on disease symptoms and patient's quality of life.


Eligibility criteria: Inclusion Criteria:

* The patient has given written informed consent prior to any study related procedures
* The patient is male or female and is aged between 18 and 75 years, inclusive,
* Diagnosis of acromegaly defined by i) GH nadir \> 1 ng/mL as assessed by an oral glucose tolerance test for non diabetic patients (central laboratory results) or a mean GH level \> 1 ng/mL based on 5 samples taken every 10 to 15 minutes for diabetic patients ( central laboratory results) AND ii) IGF-1 concentrations elevated above the age- and sex-matched normal range for diabetic and non diabetic patients (central laboratory results),
* The patient has a pituitary adenoma with a diameter greater than or equal to 10 mm based on Magnetic Resonance Imaging (MRI) central reading,
* The patient has no visual field defect identified at the visual evaluation, performed by Goldman Visual Fields Analyser and Automated visual field static perimeter, except visual field abnormality at the time of screening and that is in the investigator's Clinical judgement:

  * Not related to the pituitary adenoma
  * Clinically stable condition not presumed to change during the study period
  * Not modifying the ability to evaluate visual field changes related to the macroadenoma

Exclusion Criteria:

* The patient has a history of hypersensitivity to Lanreotide or drugs with a similar chemical structure,
* The patient has received any unlicensed drug within the 30 days prior to the screening visit or is scheduled to receive an unlicensed drug during the course of the study,
* The patient is likely to require treatment during the study with somatostatin analogues other than Lanreotide Autogel 120 mg, dopamine agonist, GH receptor antagonist (pegvisomant), and Cyclosporine or drugs that are not permitted by the study protocol,
* The patient is a female at risk of pregnancy during the study and is not using acceptable contraceptive methods. Females of childbearing potential must provide a negative pregnancy test at start of study and must be using oral, double barrier (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide), injectable contraception or an intra uterine device. Non childbearing potential is defined as post-menopause for at least 1 year, surgical sterilisation or hysterectomy at least three months before the start of the study,
* The patient is pregnant or lactating,
* The patient has a history of, or known current, problems with alcohol abuse,
* The patient has any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
* The patient has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardize the patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study,
* The patient has undergone pituitary surgery or pituitary radiotherapy prior to study entry,
* The patient has previously been treated with a somatostatin analogue,
* The patient has received a dopamine agonist or a GH receptor antagonist (pegvisomant) prior to study entry,
* The patient is expected to require pituitary surgery (adenomectomy) or to receive radiotherapy during the study period,
* Patients with suspected associated prolactinoma: prolactin level \> 100 ng/mL (central laboratory results),
* Patient is allergic to Gadolinium (MRI contrast agent) or has acute or chronic severe renal insufficiency (glomerular filtration rate \<30 mL/min/1.73m2),
* Patient known by Investigator, to have congenital or acquired optic nerve disease or any visual abnormality with risk of worsening during the course of the study (e.g glaucoma), influencing ability to evaluate Visual Field changes related to the macroadenoma.

Primary outcomes:
measure: Percentage of Patients With Relevant Reduction in Pituitary Tumour Volume (as Measured by MRI) From Baseline Volume (Visit 1) to Week 48 (After 12 Injections at Visit 5)
timeFrame: Week 1 and Week 48
Secondary outcomes:
measure: Number of Patients With at Least a 20% Reduction in Tumour Volume From Baseline Volume (Visit 1) to Week 12 (Visit 3) and Week 24 (Visit 4).
timeFrame: Baseline (week 1) to week 12 and week 24
measure: Percent Variation From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of IGF-1 Levels
timeFrame: Week 12, 24, and 48
measure: Percent Variation From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of Serum GH Levels.
timeFrame: Week 12, 24, and 48
measure: Change From Baseline to Visit 3, 4 and 5 (Week 12, 24, and 48) of Prolactin Levels
timeFrame: Week 12, 24 and 48
measure: Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Arthralgia) From Baseline
timeFrame: Week 12, 24 and 48
measure: Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Excessive Perspiration) From Baseline
timeFrame: Week 12, 24 and 48
measure: Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Fatigue) From Baseline
timeFrame: Week 12, 24 and 48
measure: Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Headache) From Baseline
timeFrame: Week 12, 24 and 48
measure: Percentage of Patients With Improved, Unchanged or Worsened Clinical Signs of Acromegaly (Soft Tissue Swelling) From Baseline
timeFrame: Week 12, 24 and 48
measure: Changes in the Global Acromegaly Quality of Life Assessment (AcroQoL) From Baseline
timeFrame: Week 12, 24 and 48
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: University Hospital Antwerpen
city: Praha
country: Czechia
facility: Všeobecná fakultní nemocnice, Karlova Univerzita
city: Helsinki
country: Finland
facility: Helsinki University Center Hospital
city: Turku
country: Finland
facility: The Turku University Central Hospital
city: Bois-Guillaume
country: France
facility: Hopital De Bois Guillaume
city: Créteil
country: France
facility: CHU Henri Mondor
city: Grenoble
country: France
facility: CHU Grenoble Albert Michallon
city: Lille
country: France
facility: CHRU Lille Hopital Claude Huriez
city: Lyon
country: France
facility: Groupement Hospitalier Est
city: Marseille
country: France
facility: Hôpital de la Timone
city: Paris
country: France
facility: Hôpital Bicêtre
city: Pessac
country: France
facility: Hopital Haut Leveque
city: Reims
country: France
facility: CHU de Reims, Hopital Robert Debré
city: Erlangen
country: Germany
facility: Friedrich-Alexander University
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität
city: Hamburg
country: Germany
facility: ENDOC Zentrum für Endokrine Tumoren und Praxis für Endokrinologie, Andrologie und medikamentöse Tumortherapie
city: München
country: Germany
facility: Medizinische Klinik Innenstadt
city: Messina
country: Italy
facility: AOU Policlinico "G. Martino" Messina
city: Napoli
country: Italy
facility: Università Federico II di Napoli, Dipartimento di Endocrinologia Molecolare e Clinicae Oncologia
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, U.O.C. di Endocrinologia
city: Rotterdam
country: Netherlands
facility: ERASMUS MC Rotterdam
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Istanbul
country: Turkey
facility: Cerrahpasa Medical Facility
city: Aberdeen
country: United Kingdom
facility: 27/28 Aberdeen Royal Infirmary
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References:
citation: Caron PJ, Bevan JS, Petersenn S, Flanagan D, Tabarin A, Prevost G, Maisonobe P, Clermont A; PRIMARYS Investigators. Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J Clin Endocrinol Metab. 2014 Apr;99(4):1282-90. doi: 10.1210/jc.2013-3318. Epub 2013 Jan 1.
citation: Caron PJ, Bevan JS, Petersenn S, Houchard A, Sert C, Webb SM; PRIMARYS Investigators Group. Effects of lanreotide Autogel primary therapy on symptoms and quality-of-life in acromegaly: data from the PRIMARYS study. Pituitary. 2016 Apr;19(2):149-57. doi: 10.1007/s11102-015-0693-y.