ACTH-producing Pituitary Tumour, Pituitary Tumor
Conditions
Keywords
Clinically non-functioning pituitary adenomas (CNFAs), silent corticotroph adenomas
Brief summary
This is a phase II, open-label, 12-month pilot study in 10 patients with silent corticotroph pituitary tumors testing the hypotheses that Pasireotide long-acting release (LAR) treatment of patients with silent corticotroph pituitary tumors and elevated plasma Proopiomelanocortin (POMC) levels will reduce plasma POMC levels and this will be associated with a reduction in pituitary tumor size. Pasireotide LAR 40 mg will be administered monthly. Baseline and monthly visits on therapy will monitor plasma levels of POMC, other pituitary function, safety labs, glucose tolerance, physical examination, and visual fields. Pituitary magnetic resonance imaging (MRI) will be done at baseline, 6 months and 12 months of therapy. The eligible patient population will consist of adult patients with known silent corticotroph pituitary tumors and elevated plasma levels of POMC.
Detailed description
Clinically non-functioning pituitary adenomas (CNFAs), the subtype of pituitary adenomas that does not appear to secrete biologically active hormone nor to have a characteristic clinical phenotype, are the most common type of pituitary macroadenoma at diagnosis. There is currently no option for medical therapy of CNFA, in general, or specifically of silent corticotroph tumors. Silent corticotroph tumors can range from being completely asymptomatic to becoming large and causing significant hypothalamic/pituitary dysfunction and visual symptoms, and most data support that this type of tumor has a more aggressive phenotype. Current therapy consists primarily of surgical removal of the tumor and for recurrent or residual tumors, repeated surgery and/or radiotherapy. In very aggressive tumors, chemotherapy has been tried with some success. Therefore, a need exists for a medical therapeutic option for the treatment of this tumor type. This project assesses this clinical need.
Interventions
DRUGPasireotide LAR
Pasireotide LAR (SIGNIFOR® LAR) is a somatostatin analog indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option. It is a long acting release injectable suspension for intramuscular use. The starting dose is Pasireotide LAR 40 mg/month intramuscular (IM), this will be increased to 60 mg/month at 6 months if a fall in POMC levels and/or tumor shrinkage are not attained.
Sponsors
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Adults (males and females) with a diagnosis of a clinically nonfunctioning pituitary tumor of the silent corticotroph tumor type (i.e., positive adrenocorticotropin (ACTH) staining on immunohistochemical staining of the pituitary tumor obtained at surgery) 2. Plasma POMC level \> upper limit of normal 3. Prior pituitary tumor surgery with residual or recurrent pituitary tumor visible on MRI scan that is ≥ 5 mm from the optic chiasm. 4. Surgical resection of the pituitary adenoma must have occurred two or more months prior to enrollment 5. If patients have undergone pituitary radiotherapy they must have completed their course of radiotherapy at least 2 months prior to study screening 6. No prior somatostatin analog therapy 7. No concurrent use of dopamine agonist therapy 8. No active malignancy 9. Stable pituitary hormone supplements (x 2 months) prior to baseline visit 10. Sign and date an informed consent document indicating that the subject has been informed of and agrees to all pertinent aspects of the trial
Exclusion criteria
Subjects must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma Proopiomelanocortin (POMC) Levels | Baseline, 12 months | This is to measure the effect of Pasireotide LAR (long-acting release) treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pituitary Tumor Volume | Baseline, 12 months | This is to measure the effect of Pasireotide LAR (long-acting release) treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pasireotide LAR Therapy Subjects will receive Pasireotide LAR monthly. Safety labs and Pituitary MRI will be performed.
Pasireotide LAR: Pasireotide LAR (SIGNIFOR® LAR) is a somatostatin analog indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option. It is a long acting release injectable suspension for intramuscular use.
The starting dose is Pasireotide LAR 40 mg/month intramuscular (IM), this will be increased to 60 mg/month at 6 months if a fall in POMC levels and/or tumor shrinkage are not attained. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Pasireotide LAR Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Change in Plasma Proopiomelanocortin (POMC) Levels
This is to measure the effect of Pasireotide LAR (long-acting release) treatment.
Time frame: Baseline, 12 months
Population: The study was terminated due to poor enrollment. The data was not collected or analyzed.
Secondary
Change in Pituitary Tumor Volume
This is to measure the effect of Pasireotide LAR (long-acting release) treatment.
Time frame: Baseline, 12 months
Population: The study was terminated due to poor enrollment. The data was not collected or analyzed.