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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Medical treatment by Octreotide LAR | Active Comparator | Medical therapy with Octreotide LAR 30 mg/month for 3 months preceding surgery |
|
| Surgical debulking followed by Octreotide LAR | Active Comparator | Surgical debulking of pituitary tumor followed by Octreotide LAR if not surgically cured |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Octreotide LAR | Drug |
| ||
| transsphenoidal surgery |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David M Kleinberg, MD | NYU School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New York University School of Medicine | New York | New York | 10016 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Medical Treatment by Octreotide LAR | Medical therapy with Octreotide LAR 30 mg/month for 3 months preceding surgery Octreotide LAR |
| FG001 | Surgical Debulking Followed by Octreotide LAR | Surgical debulking of pituitary tumor followed by Octreotide LAR if not surgically cured Octreotide LAR transsphenoidal surgery |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Medical Treatment by Octreotide LAR | Medical therapy with Octreotide LAR 30 mg/month for 3 months preceding surgery Octreotide LAR |
| BG001 | Surgical Debulking Followed by Octreotide LAR |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 3 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Medical Treatment by Octreotide LAR | Medical therapy with Octreotide LAR 30 mg/month for 3 months preceding surgery Octreotide LAR |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyponatremia with Abdominal Discomfort | General disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea/Vomiting/Diarrhea/Bloating/Constipation/GI distress | Gastrointestinal disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Kleinberg | NYU Langone Medical Center | 212 263 6772 | David.Kleinberg@nyumc.org |
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| ID | Term |
|---|---|
| D010911 | Pituitary Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D007029 | Hypothalamic Neoplasms |
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| Procedure |
|
Surgical debulking of pituitary tumor followed by Octreotide LAR if not surgically cured
Octreotide LAR
transsphenoidal surgery
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 3 months |
|
|
|
| Secondary | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 3 months |
|
|
|
| 0 |
| 15 |
| 5 |
| 15 |
| EG001 | Surgical Debulking Followed by Octreotide LAR | Surgical debulking of pituitary tumor followed by Octreotide LAR if not surgically cured Octreotide LAR transsphenoidal surgery | 1 | 26 | 12 | 26 |
| Headaches | Nervous system disorders |
|
| Pain at the Injection site | Surgical and medical procedures |
|
| Otitis Media | Ear and labyrinth disorders |
|
| Seizures (Seizure disorder since childhood) | Nervous system disorders |
|
| Dry nose | General disorders |
|
| Fatigue | General disorders |
|
| Back Pain | Musculoskeletal and connective tissue disorders |
|
| Urinary Tract Infection | Renal and urinary disorders |
|
| Respiratory Infections/Cold symptoms/ Cough | Infections and infestations |
|
| Sinus irritation/pressure | General disorders |
|
| Thyroiditis | Endocrine disorders |
|
| Dizziness | General disorders |
|
| Nosebleed | Respiratory, thoracic and mediastinal disorders |
|
| Arm Weakness/Numbing | General disorders |
|
| Muscle ache | General disorders |
|
| Depression | Psychiatric disorders |
|
| Planned excision of occipital skin tumor | Surgical and medical procedures |
|
| Joint Pain | Musculoskeletal and connective tissue disorders |
|
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| D015173 |
| Supratentorial Neoplasms |
| D001932 | Brain Neoplasms |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D007027 | Hypothalamic Diseases |
| D010900 | Pituitary Diseases |
| D004700 | Endocrine System Diseases |