Pasireotide LAR and Pegvisomant Study in Acromegaly

Acromegaly Clinical Trial

— PAPE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02668172
• Other study ID #: NL49517.078.14
• Secondary ID: 2014-002219-41NT
• Status: Active, not recruiting
• Phase: Phase 4
• First received: December 7, 2015
• Last updated: August 2, 2016
• Start date: August 2015
• Est. completion date: June 2017

Study information

• Verified date: August 2016
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: June 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acromegaly

Intervention

Drug:
• Pasireotide LAR 60 mg
as mono-therapy or in combination with pegvisomant
• Pegvisomant
only in combination with pasireotide LAR

Locations

Country	Name	City	State
Netherlands	Erasmus Medical Center	Rotterdam	South Holland

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	Novartis

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		24 weeks	No
Secondary	The proportion of patients with normalized IGF1 levels after 48 weeks of pasireotide LAR monotherapy		48 weeks	No
Secondary	The proportion of patients with normalized IGF1 levels after 48 weeks combination treatment of pasireotide LAR with weekly pegvisomant.		48 weeks	No
Secondary	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		48 weeks	No
Secondary	Change in tumor volume by pituitary MRI		Baseline and 48 weeks	Yes
Secondary	Tolerability and safety profile of pasireotide Long Acting Release (LAR) monotherapy	Toxicity will be assessed using the National Cancer Institute-Common Toxicology Criteria Adverse Events version 4 (NCI-CTCAE v.4.03) and for laboratory assessments that include biochemistry, hematology, urinalysis; special safety assessments that include the regular monitoring and recording of blood glucose, insulin, HbA1c, GH and IGF-1, thyroid and liver function tests, gallbladder examinations and ECGs. Concomitant medications/Significant nondrug therapies will be assessed from study enrollment until the safety follow-up.	48 weeks	Yes
Secondary	Tolerability and safety profile of pasireotide LAR and pegvisomant combination therapy	Toxicity will be assessed using the National Cancer Institute-Common Toxicology Criteria Adverse Events version 4 (NCI-CTCAE v.4.03) and for laboratory assessments that include biochemistry, hematology, urinalysis; special safety assessments that include the regular monitoring and recording of blood glucose, insulin, HbA1c, and IGF-1, thyroid and liver function tests, gallbladder examinations and ECGs. Concomitant medications/Significant nondrug therapies will be assessed from study enrollment until the safety follow-up.	48 weeks	Yes
Secondary	Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly	AcroQol is quality of life questionnaire specifically designed for acromegaly	Change in scores as measured by AcroQoL from baseline to week 48	No
Secondary	Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly	PASQ are questionnaire for the disease specific symptoms	Change in scores as measured by PASQ from baseline to week 48	No
Secondary	Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly		Description of signs and symptoms of acromegaly	No
Secondary	Evaluation of body composition by Dual-energy X-ray Absorptiometry (DEXA) scan		baseline and 48 weeks	No

External Links

•   Summary of study at Dutch Trial Register
•   Summary of study at the WHO International Clinical Trials Registry Platform