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Pasireotide LAR and Pegvisomant Study in Acromegaly (PAPE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02668172
Recruitment Status : Unknown
Verified August 2016 by s neggers, Erasmus Medical Center.
Recruitment status was:  Active, not recruiting
First Posted : January 29, 2016
Last Update Posted : August 3, 2016
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
s neggers, Erasmus Medical Center

Study Description
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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.

Condition or disease Intervention/treatment Phase
Acromegaly Drug: Pasireotide LAR 60 mg Drug: Pegvisomant Phase 4

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : August 2015
Estimated Primary Completion Date : March 2017
Estimated Study Completion Date : June 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.

 Drug: Pasireotide LAR 60 mg
as mono-therapy or in combination with pegvisomant
Other Name: Signifor, SOM230
Experimental: 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.
 Drug: Pasireotide LAR 60 mg
as mono-therapy or in combination with pegvisomant
Other Name: Signifor, SOM230

Drug: Pegvisomant
only in combination with pasireotide LAR
Other Name: Somavert
Experimental: 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.

 Drug: Pasireotide LAR 60 mg
as mono-therapy or in combination with pegvisomant
Other Name: Signifor, SOM230

Drug: Pegvisomant
only in combination with pasireotide LAR
Other Name: Somavert


Outcome Measures
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Primary Outcome Measures :
  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 [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. The proportion of patients with normalized IGF1 levels after 48 weeks of pasireotide LAR monotherapy [ Time Frame: 48 weeks ]
  2. The proportion of patients with normalized IGF1 levels after 48 weeks combination treatment of pasireotide LAR with weekly pegvisomant. [ Time Frame: 48 weeks ]
  3. 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 [ Time Frame: 48 weeks ]
  4. Change in tumor volume by pituitary MRI [ Time Frame: Baseline and 48 weeks ]
  5. Tolerability and safety profile of pasireotide Long Acting Release (LAR) monotherapy [ Time Frame: 48 weeks ]
    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.

  6. Tolerability and safety profile of pasireotide LAR and pegvisomant combination therapy [ Time Frame: 48 weeks ]
    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.

  7. Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly [ Time Frame: Change in scores as measured by AcroQoL from baseline to week 48 ]
    AcroQol is quality of life questionnaire specifically designed for acromegaly

  8. Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly [ Time Frame: Change in scores as measured by PASQ from baseline to week 48 ]
    PASQ are questionnaire for the disease specific symptoms

  9. Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly [ Time Frame: Description of signs and symptoms of acromegaly ]
  10. Evaluation of body composition by Dual-energy X-ray Absorptiometry (DEXA) scan [ Time Frame: baseline and 48 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02668172


Locations
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Netherlands
Erasmus Medical Center
Rotterdam, South Holland, Netherlands, 3000CA
Sponsors and Collaborators
Erasmus Medical Center
Novartis
Investigators
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Principal Investigator: Sebastian Neggers, MD PhD Erasmus MC
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: s neggers, Consultant endocrinology, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02668172    
Other Study ID Numbers: NL49517.078.14
2014-002219-41 ( EudraCT Number )
NTR5282 ( Registry Identifier: Dutch Trial Register )
First Posted: January 29, 2016    Key Record Dates
Last Update Posted: August 3, 2016
Last Verified: August 2016
Keywords provided by s neggers, Erasmus Medical Center:
pegvisomant
pasireotide LAR
long acting somatostatin analogues
Additional relevant MeSH terms:
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Acromegaly
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
 Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Pasireotide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs