Surgical Debulking of Pituitary Adenomas

Does Surgical Debulking Of Pituitary Adenomas Improve Responsiveness To Octreotide LAR In The Treatment Of Acromegaly: An Investigator-Initiated Study

This is a randomized, multicenter trial with stratification done by a single radiologist at the coordinating center (NYU), and patients with comparable disease will be randomized to Sandostatin LAR treatment administered 1 time per month by IM injection for 3 months before (Arm A) or, for non-cured patients, after (Arm B) surgery. All patients will undergo transsphenoidal hypophysectomy. The impact of surgical debulking on responsiveness to Sandostatin LAR will be evaluated.The primary objective of this trial will be to determine whether surgery (debulking of pituitary adenomas) improves the response of patients with acromegaly to treatment with Octreotide LAR, when compared to Octreotide LAR therapy alone.

Study Overview

• Status: Completed
• Conditions: Pituitary Adenoma
• Intervention / Treatment: Drug: Octreotide LAR; Procedure: transsphenoidal surgery

Detailed Description

The current goal of treatment for people with acromegaly is normalization of both growth hormone (GH) and insulin-like-growth-factor-1 (IGF-1) levels. Normalization of GH and IGF-1 levels attenuates the morbidity (hypertension, cardiovascular disease, sleep apnea, increased cancer risk, arthritis) and increased mortality associated with persistent GH and IGF-1 elevation. The optimal approach to achieving these goals in patients with pituitary macroadenomas remains controversial. Available treatment modalities include transsphenoidal hypophysectomy, medical therapy (somatostatin analogues and/or dopaminergic agonists), radiotherapy, or a combination or these interventions. No randomized trials have been conducted to investigate whether surgical debulking of pituitary macroadenomas enhances the efficacy of medical therapy. This study is designed to rigorously investigate whether surgical debulking increases the efficacy of a long-acting depot somatostatin preparation, Sandostatin LAR, so that evidence-based optimal care may be offered to patients with acromegaly.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Carry a diagnosis of de novo acromegaly with an elevated age and sex matched IGF-I and GH >1ng/ml at all time points during OGTT
• Have a pituitary macroadenoma
• Have clinical changes consistent with acromegaly
• Have a single random serum hGH of 12.5 ng/ml or greater
• Both the endocrinologist and surgeon must agree that the patient's health would not be compromised by a three-month period during which time Octreotide LAR is administered.
• Patients currently on dopamine agonist who agree to discontinue medication (2-6 week washout required)

Exclusion Criteria:

• Pregnant or breastfeeding
• Documented loss of vision due to pituitary tumor
• Prior treatment for acromegaly other than dopamine agonists
• Inability to complete the protocol
• Intolerance to octreotide

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Medical treatment by Octreotide LAR; Medical therapy with Octreotide LAR 30 mg/month for 3 months preceding surgery	Drug: Octreotide LAR
Active Comparator: Surgical debulking followed by Octreotide LAR; Surgical debulking of pituitary tumor followed by Octreotide LAR if not surgically cured	Drug: Octreotide LAR; Procedure: transsphenoidal surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders (Primary Medical Treatment in Arm 1, Primary Surgical Treatment in Arm 2)	Nadir growth hormone <1 ng/mL during a standard 2 hour oral glucose tolerance test using 75 g glucose and normal IGF-I according to age and gender-matched standards.	3 months
Percentage of Responders (All Treatments)	Nadir growth hormone <1 ng/mL during a standard 2 hour oral glucose tolerance test using 75 g glucose and normal IGF-I according to age and gender-matched standards.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders (Only Including Surgical Failures in Arm 2)	Nadir growth hormone <1 ng/mL during a standard 2 hour oral glucose tolerance test using 75 g glucose and normal IGF-I according to age and gender-matched standards.	3 months

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: David M Kleinberg, MD, NYU School of Medicine

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: June 9, 2011
• First Submitted That Met QC Criteria: June 10, 2011
• First Posted (Estimate): June 13, 2011

Study Record Updates

• Last Update Posted (Estimate): August 29, 2016
• Last Update Submitted That Met QC Criteria: July 25, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Adenoma; Pituitary Neoplasms; Pituitary Diseases; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: R11104