Acromegaly Combination Treatment Study

• ClinicalTrials.gov Identifier: NCT01538966
• Recruitment Status: Recruiting
• First Posted: February 27, 2012
• Last Update Posted: October 1, 2020
• Sponsor: Cedars-Sinai Medical Center
• Information provided by (Responsible Party): Shlomo Melmed, MD, Cedars-Sinai Medical Center

Study Description

Brief Summary:

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 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.

Condition or disease	Intervention/treatment	Phase
Acromegaly	Drug: Pegvisomant; Drug: Octreotide LAR; Drug: Lanreotide	Not Applicable

Detailed Description:

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 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. An MRI will be performed at the conclusion of the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparison of Combination Low-Dose SRL + Daily Pegvisomant Therapy, Low-Dose SRL + Weekly Pegvisomant Therapy, and High-Dose SRL + Weekly Pegvisomant Therapy
• Study Start Date: January 2012
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: June 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: High dose SRL + weekly Pegvisomant; High dose of SRL monthly; Octreotide LAR 30mg; Lanreotide 120mg Weekly Pegviosmant (40-120mg/week)	Drug: Pegvisomant; Other Name: Somavert; Drug: Octreotide LAR; Other Name: Sandostatin; Drug: Lanreotide; Other Name: Somatuline
Active Comparator: Low dose SRL + daily Pegvisomant; Low dose of SRL monthly; Octreotide LAR 10mg; Lanreotide 60mg Daily Pegviosmant (15-60mg/day)	Drug: Pegvisomant; Other Name: Somavert; Drug: Octreotide LAR; Other Name: Sandostatin; Drug: Lanreotide; Other Name: Somatuline
Active Comparator: Low dose SRL + weekly Pegvisomant; Low dose of SRL monthly; Octreotide LAR 10mg; Lanreotide 60mg Weekly Pegviosmant (40-120mg/week)	Drug: Pegvisomant; Other Name: Somavert; Drug: Octreotide LAR; Other Name: Sandostatin; Drug: Lanreotide; Other Name: Somatuline

Outcome Measures

Primary Outcome Measures :

1. Equivalent Control [ Time Frame: 12 months ]
   We will evaluate whether combination low dose SRL and weekly or daily Pegvisomant will attain equivalent control of serum IGF-1 levels at a lowerr cost, compared to combination high dose SRL and weekly pegvisomant; lower doses of therapy will greatly reduce the cost of acromegaly therapy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Vivian Hwe; 424-315-4489; hwev@cshs.org

Locations

United States, California

Cedars-Sinai Medical Center; Recruiting

Los Angeles, California, United States, 90048

Sub-Investigator: Vivien Bonert, MD

Sponsors and Collaborators

Cedars-Sinai Medical Center

Investigators

• Principal Investigator: Shlomo Melmed, MD; Cedars-Sinai Medical Center

More Information

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

Bonert V, Mirocha J, Carmichael J, Yuen KCJ, Araki T, Melmed S. Cost-Effectiveness and Efficacy of a Novel Combination Regimen in Acromegaly: A Prospective, Randomized Trial. J Clin Endocrinol Metab. 2020 Sep 1;105(9). pii: dgaa444. doi: 10.1210/clinem/dgaa444.

• Responsible Party: Shlomo Melmed, MD, Executive Vice President, Academic Affairs, Cedars-Sinai Medical Center
• ClinicalTrials.gov Identifier: NCT01538966
• Other Study ID Numbers: Pro26424; WS2036536 ( Other Grant/Funding Number: Pfizer )
• First Posted: February 27, 2012
• Last Update Posted: October 1, 2020
• Last Verified: September 2020

Keywords provided by Shlomo Melmed, MD, Cedars-Sinai Medical Center:

acromegaly; pituitary; pegvisomant; somavert; lanreotide; octreotide

Additional relevant MeSH terms:

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; Octreotide; Lanreotide; Angiopeptin; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents