Clinical trial NCT02668172: Pasireotide LAR and Pegvisomant Study in Acromegaly
Official title: Efficacy and Safety of Pasireotide Long Acting Release (LAR) in Combination With Weekly Pegvisomant in Previously Controlled Acromegaly Patients on Combination Treatment of Long-Acting Somatostatin Analogues and Weekly Pegvisomant
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acromegaly
Keywords: pegvisomant
pasireotide LAR
long acting somatostatin analogues
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2016-01-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the efficacy of Pasireotide Long Acting Release (LAR) alone and in combination with weekly Pegvisomant (PEGV) in acromegaIy patients previously controlled with combination treatment of long-acting Somatostatin analogs (LA-SSAs) and PEGV.

Detailed description: Pasireotide Long Acting Release (Signifor ®), a novel long-acting multi-receptor ligand somatostatin analogue, has been shown to be more effective for the treatment of GH-secreting pituitary adenomas than currently used long-acting somatostatin analogues (LA-SSAs). The long-term efficacy of acromegaly patients using LA-SSAs in combination with PEGV was over 90% in terms of normalization of IGF-I. The combination of PEGV with pasireotide LAR has not been studied yet. Combining PEGV with pasireotide LAR could result in a lower dose and less injections of pegvisomant. This may ultimately lead to a more cost-effective treatment and improved quality of life.

Eligibility criteria: Inclusion Criteria:

* written informed consent male or female aged ≥ 18 years
* documentation supporting the diagnosis of acromegaly based on elevated GH and/or IGF-I levels due to a pituitary tumor
* the patient is treated with lanreotide Autogel or octreotide LAR and PEGV (twice) weekly for at least 6 months and has a serum IGF-I level within 120 % of the age adjusted normal limits. These patients were previously not controlled by somatostatin analogs alone.
* female of no childbearing potential or male. No childbearing potential is defined as being postmenopausal for at least 1 year, or women with documented infertility (natural or acquired) or using two acceptable contraceptive measures, except for oral contraceptives.
* male subjects must agree that, if their partner is at risk of becoming pregnant, they will use a medically accepted, effective method of contraception (i.e. use a condom) for the duration of the study
* subjects must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow up evaluation as specified in the protocol.

Exclusion Criteria:

Patients will not be included in the study if he or she:

* has undergone pituitary surgery or radiotherapy within 6 months prior to study entry.
* it is anticipated that the patient will receive pituitary surgery or radiotherapy during the study.
* has a history of hypersensitivity to lanreotide, octreotide or pegvisomant or drugs with a similar chemical structure
* has been treated with any unlicensed drug within the last 30 days before study entry.
* has abnormal hepatic function at study entry (defined as AST, ALT, gGT, alkaline phosphatase, or total bilirubin above 3 ULN)
* is at risk of pregnancy or is lactating. Females of childbearing potential must provide a negative pregnancy test within 5 days before the start of the study and must be using contraception. Non-childbearing potential is defined as post-menopause for at least one year, surgical sterilization or hysterectomy at least three months before the start of the study.
* has a history of, or known current problems with alcohol or drug abuse.
* has a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
* has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the subject's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study.
* renal insufficiency, clearance \< 50ml/min
* poorly controlled diabetes mellitus with an HbA1c \> 9.0%
* patients with a QTc \> 500 ms on the EKG
* participation in a clinical trial in the last 6 months

Primary outcomes:
measure: The proportion of patients with normalized IGF1 levels at 24 weeks in the pasireotide LAR monotherapy group and in the pasireotide LAR combined with pegvisomant group
timeFrame: 24 weeks
Secondary outcomes:
measure: The proportion of patients with normalized IGF1 levels after 48 weeks of pasireotide LAR monotherapy
timeFrame: 48 weeks
measure: The proportion of patients with normalized IGF1 levels after 48 weeks combination treatment of pasireotide LAR with weekly pegvisomant.
timeFrame: 48 weeks
measure: The necessary dose of pegvisomant during combination treatment of pasireotide LAR with pegvisomant in patients with an IGF-I level within the age adjusted normal limits
timeFrame: 48 weeks
measure: Change in tumor volume by pituitary MRI
timeFrame: Baseline and 48 weeks
measure: Tolerability and safety profile of pasireotide Long Acting Release (LAR) monotherapy
timeFrame: 48 weeks
measure: Tolerability and safety profile of pasireotide LAR and pegvisomant combination therapy
timeFrame: 48 weeks
measure: Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly
timeFrame: Change in scores as measured by AcroQoL from baseline to week 48
measure: Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly
timeFrame: Change in scores as measured by PASQ from baseline to week 48
measure: Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly
timeFrame: Description of signs and symptoms of acromegaly
measure: Evaluation of body composition by Dual-energy X-ray Absorptiometry (DEXA) scan
timeFrame: baseline and 48 weeks
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: South Holland
Study officials:
affiliation: Erasmus Medical Center
name: Sebastian Neggers, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muhammad A, van der Lely AJ, Delhanty PJD, Dallenga AHG, Haitsma IK, Janssen JAMJL, Neggers SJCMM. Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Controlled With Pegvisomant and First-Generation Somatostatin Analogues (PAPE Study). J Clin Endocrinol Metab. 2018 Feb 1;103(2):586-595. doi: 10.1210/jc.2017-02017.