Pituitary Adenoma
Conditions
Brief summary
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
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.
Interventions
DRUGOctreotide LAR
PROCEDUREtranssphenoidal surgery
Sponsors
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders (Primary Medical Treatment in Arm 1, Primary Surgical Treatment in Arm 2) | 3 months | 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. |
| Percentage of Responders (All Treatments) | 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders (Only Including Surgical Failures in Arm 2) | 3 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Medical Treatment by Octreotide LAR Medical therapy with Octreotide LAR 30 mg/month for 3 months preceding surgery
Octreotide LAR | 15 |
| Surgical Debulking Followed by Octreotide LAR Surgical debulking of pituitary tumor followed by Octreotide LAR if not surgically cured
Octreotide LAR
transsphenoidal surgery | 26 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Medical Treatment by Octreotide LAR | Surgical Debulking Followed by Octreotide LAR | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 25 Participants | 39 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian or Pacific Islander | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Black, Not of Hispanic-American Origin | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic-American | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Other or Unknown | 3 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized White, not of Hispanic-American Origin | 10 participants | 21 participants | 31 participants |
| Region of Enrollment Germany | 5 participants | 8 participants | 13 participants |
| Region of Enrollment Italy | 2 participants | 4 participants | 6 participants |
| Region of Enrollment United States | 8 participants | 14 participants | 22 participants |
| Sex: Female, Male Female | 5 Participants | 12 Participants | 17 Participants |
| Sex: Female, Male Male | 10 Participants | 14 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 15 | 12 / 26 |
| serious Total, serious adverse events | 0 / 15 | 1 / 26 |
Outcome results
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.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medical Treatment by Octreotide LAR | Percentage of Responders (All Treatments) | 6.7 percentage of participants |
| Surgical Debulking Followed by Octreotide LAR | Percentage of Responders (All Treatments) | 76.9 percentage of participants |
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.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medical Treatment by Octreotide LAR | Percentage of Responders (Primary Medical Treatment in Arm 1, Primary Surgical Treatment in Arm 2) | 6.7 percentage of participants |
| Surgical Debulking Followed by Octreotide LAR | Percentage of Responders (Primary Medical Treatment in Arm 1, Primary Surgical Treatment in Arm 2) | 50 percentage of participants |
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.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medical Treatment by Octreotide LAR | Percentage of Responders (Only Including Surgical Failures in Arm 2) | 6.7 percentage of participants |
| Surgical Debulking Followed by Octreotide LAR | Percentage of Responders (Only Including Surgical Failures in Arm 2) | 53.9 percentage of participants |