Acromegaly Combination Treatment Study

Study Overview
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Brief Summary
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In this study the investigators will evaluate whether combination low dose somatostatin receptor ligand (SRL) and weekly or daily pegvisomant will attain equivalent control of serum insulin-like growth factor (IGF)-1 levels at a lower cost, compared to combination high dose SRL and weekly pegvisomant. Lower doses of therapy will greatly reduce cost of acromegaly therapy.

Detailed Description
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Subjects will be stratified based on prior response to SRL therapy and then randomized to one of three treatment arms. The study will begin when the combination of octreotide long-acting release (LAR) or lanreotide and pegvisomant is first administered. Study visits will occur every 4 weeks from the start of the study. However, for subjects who cannot make every study visit due to distance, the study team will facilitate monthly blood draws at their local Quest laboratory facility. After the 24 weeks of combination therapy, subjects with a controlled IGF-1 will then start pegvisomant monotherapy at the same dose and schedule that they attained normalization in combination therapy. IGF-1 levels, liver function test, and blood glucose will be performed monthly. Magnetic resonance imaging (MRI) will be performed at the conclusion of the study.

Official Title
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Comparison of Combination Low-Dose SRL + Daily Pegvisomant Therapy, Low-Dose SRL + Weekly Pegvisomant Therapy, and High-Dose SRL + Weekly Pegvisomant Therapy

Conditions
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Acromegaly

Intervention / Treatment
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* Drug: Pegvisomant
* Drug: Octreotide LAR
* Drug: Lanreotide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed patients with acromegaly who have not had surgery or medical therapy Acromegaly patients who are at least 3 months post surgery, who are/are not receiving adjuvant medical therapy Acromegaly patients on SRL monotherapy with normal or elevated IGF-1 levels Acromegaly patients on Pegvisomant monotherapy with normal or elevated IGF-1 levels. Acromegaly patients who have received SRL and dopamine agonist therapy, after a 6 week washout period of the dopamine agonist. Acromegaly patients on combination therapy with maximum doses of SRL and Pegvisomant (daily or weekly Normal liver function tests before randomization to treatment The patient has had appropriate dynamic testing of the pituitary axis and, if applicable, is receiving appropriate hormone replacement therapy. Exclusion Criteria: The patient harbors a macroadenoma with visual field defects due to chiasmatic compression The patient has clinically significant hepatic abnormalities and/or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) above 3 times the upper limit of normal at the baseline visit. The patient had pituitary surgery within 3 months prior to study entry The patient had radiotherapy within 12 months prior to study entry The patient has abnormal CBC and chemistry panel at the baseline visit, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the patient's safety. The patient has a known hypersensitivity to any of the test materials or related compounds. The patient has a history of, or known current problems with alcohol or drug abuse. The patient has any mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study, and/or evidence of an uncooperative attitude.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High dose SRL + weekly Pegvisomant<br>High dose of SRL monthly Octreotide LAR 30mg Lanreotide 120mg Weekly Pegvisomant (40-120mg/week) | Drug: Pegvisomant<br> <br> * Other names: Somavert;Drug: Octreotide LAR<br> <br> * Other names: Sandostatin;Drug: Lanreotide<br> <br> * Other names: Somatuline;|
| Active Comparator: Low dose SRL + daily Pegvisomant<br>Low dose of SRL monthly Octreotide LAR 10mg Lanreotide 60mg Daily Pegvisomant (15-60mg/day) | Drug: Pegvisomant<br> <br> * Other names: Somavert;Drug: Octreotide LAR<br> <br> * Other names: Sandostatin;Drug: Lanreotide<br> <br> * Other names: Somatuline;|
| Active Comparator: Low dose SRL + weekly Pegvisomant<br>Low dose of SRL monthly Octreotide LAR 10mg Lanreotide 60mg Weekly Pegvisomant (40-120mg/week) | Drug: Pegvisomant<br> <br> * Other names: Somavert;Drug: Octreotide LAR<br> <br> * Other names: Sandostatin;Drug: Lanreotide<br> <br> * Other names: Somatuline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost Effectiveness | We evaluated cost-effectiveness of combination low-dose SRL and weekly or daily pegvisomant compared to combination high-dose SRL and weekly pegvisomant by assessing cost of therapy per month in each treatment arm among patients who achieved normal IGF-1 levels. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acromegaly, pituitary, pegvisomant, somavert, lanreotide, octreotide