Pasireotide LAR and Pegvisomant Study in Acromegaly

NCT ID: NCT02668172

Last Updated: 2016-08-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2017-06-30

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.

Conditions

Acromegaly

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pasireotide LAR 60 mg monotherapy week 12

After enrollment, acromegaly patients on combination treatment will half their regular weekly dose of pegvisomant (PEGV) for 12 weeks (run-in period).

When insuline-like growth factor 1 (IGF-I) remains within the age adjusted normal limits after 12 weeks, PEGV and the LA-SSA (Octreotide Long Acting Release (LAR) or Lanreotide Autogel) with Pegvisomant (PEGV) are discontinued and patients are switched to pasireotide LAR 60 mg for 12 weeks.

Group Type: EXPERIMENTAL

Pasireotide LAR 60 mg

Intervention Type: DRUG

as mono-therapy or in combination with pegvisomant

Pasireotide LAR 60 mg and Pegvisomant week 12

When IGF-I rises above the adjusted normal limits after 12 weeks (run-in period), these subjects will switch their LA-SSA to Pasireotide LAR 60 mg every 4 weeks and continue with the reduced PEGV dose of the run-in period, for the remaining 12 weeks.

Group Type: EXPERIMENTAL

Pasireotide LAR 60 mg

Intervention Type: DRUG

as mono-therapy or in combination with pegvisomant

Pegvisomant

Intervention Type: DRUG

only in combination with pasireotide LAR

Pasireotide LAR 60 mg and Pegvisomant week 24

Between week 12 and 24 dose adaptations of PEGV are not permitted unless IGF-I drops below the age adjusted normal limits, then the dose of PEGV will be decreased stepwise with 20 mg weekly until IGF-I is within the age adjusted normal limits.

At week 24, efficacy will be assessed, as the number of patients with a normal IGF-I in the two different groups; the combination Pasireotide LAR 60 mg / PEG V dose and monotherapy Pasireotide LAR 60 mg.

From week 24 patients will continue with Pasireotide LAR 60 mg monotherapy, or Pasireotide LAR will be combined with 50% of the original dose of PEGV, or with an increasing dose of PEGV every 8 weeks depending on the treatment arm.

Group Type: EXPERIMENTAL

Pasireotide LAR 60 mg

Intervention Type: DRUG

as mono-therapy or in combination with pegvisomant

Pegvisomant

Intervention Type: DRUG

only in combination with pasireotide LAR

Interventions

Pasireotide LAR 60 mg

as mono-therapy or in combination with pegvisomant

Intervention Type: DRUG

Pegvisomant

only in combination with pasireotide LAR

Intervention Type: DRUG

Other Intervention Names

Signifor, SOM230; Somavert

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

s neggers

Consultant endocrinology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sebastian Neggers, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 29155991 (View on PubMed)

Related Links

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NTR5282

Summary of study at the WHO International Clinical Trials Registry Platform

Other Identifiers

2014-002219-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NTR5282

Identifier Type: REGISTRY

Identifier Source: secondary_id

NL49517.078.14

Identifier Type: -

Identifier Source: org_study_id