Pasireotide LAR and Pegvisomant Study in Acromegaly

NCT02668172 | Unknown Phase 4 DMC

• 3 other identifiers: NL49517.078.142014-002219-41NTR5282
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Acromegaly

Keywords

pegvisomant; pasireotide LAR; long acting somatostatin analogues

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (10)

• The proportion of patients with normalized IGF1 levels after 48 weeks of pasireotide LAR monotherapy

  48 weeks

• The proportion of patients with normalized IGF1 levels after 48 weeks combination treatment of pasireotide LAR with weekly pegvisomant.

  48 weeks

• 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

• Change in tumor volume by pituitary MRI

  Baseline and 48 weeks

• Tolerability and safety profile of pasireotide Long Acting Release (LAR) monotherapy

  48 weeks

Study Arms (3)

Pasireotide LAR 60 mg monotherapy week 12

EXPERIMENTAL

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.

Drug: Pasireotide LAR 60 mg

Pasireotide LAR 60 mg and Pegvisomant week 12

EXPERIMENTAL

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.

Drug: Pasireotide LAR 60 mg; Drug: Pegvisomant

Pasireotide LAR 60 mg and Pegvisomant week 24

EXPERIMENTAL

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.

Drug: Pasireotide LAR 60 mg; Drug: Pegvisomant

Interventions

Pasireotide LAR 60 mg DRUG

as mono-therapy or in combination with pegvisomant

Also known as: Signifor, SOM230

Pasireotide LAR 60 mg and Pegvisomant week 12; Pasireotide LAR 60 mg and Pegvisomant week 24; Pasireotide LAR 60 mg monotherapy week 12

Pegvisomant DRUG

only in combination with pasireotide LAR

Also known as: Somavert

Pasireotide LAR 60 mg and Pegvisomant week 12; Pasireotide LAR 60 mg and Pegvisomant week 24

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Novartis: collaborator

Study Sites (1)

Erasmus Medical Center

Rotterdam, South Holland, 3000CA, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 29155991 DERIVED

Related Links

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

MeSH Terms

Conditions

Acromegaly

Interventions

pasireotide; pegvisomant

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Officials

• Sebastian Neggers, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant endocrinology

Study Record Dates

• First Submitted: December 7, 2015
• First Posted: January 29, 2016
• Study Start: August 1, 2015
• Primary Completion: March 1, 2017
• Study Completion: June 1, 2017
• Last Updated: August 3, 2016

Record last verified: 2016-08

Locations

NL (1)