Surgical Debulking of Pituitary Adenomas

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pituitary Adenoma

Intervention / Treatment
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* Drug: Octreotide LAR
* Procedure: transsphenoidal surgery


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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

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


Arms and Interventions

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

What is the study measuring?
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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 |