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There are no available medical treatment options for patients with non-functioning pituitary adenomas (NFPA) or with resistant prolactinomas to dopamine agonists (DA) who are not cured by surgery. The study of the receptors by quantitative messenger ribonucleic acid (mRNA) expression levels and immunohistochemistry analysis might end with a better understanding of these tumors. Besides that, it will be assessed the in vitro and in vivo responses to pasireotide (for NFPA and prolactinomas) and cabergoline (for NFPA). These responses will be compared with the receptor expressions which may be a tool as a predicting element of the response to these compounds.
The goals of this study are: to verify whether cabergoline and pasireotide are effective in NFPA to control tumor re-growth as adjuvant therapy after neurosurgery and whether pasireotide is capable of normalizing the prolactin levels in patients with prolactinomas resistant to cabergoline; to assess the mRNA levels of dopamine receptor type 2 (DR2) and SSTR1-5 and their protein expression; to evaluate the in vitro hormonal response to cabergoline, octreotide and pasireotide; and to determine whether the mRNA DR2/SSTR1-5 and/or protein expression and/or in vitro hormonal response to cabergoline, octreotide and pasireotide correlates with the in vivo response to the former and to the last one. With this data the investigators intend to establish if the mRNA analysis and/or protein expression in NFPA and resistant prolactinomas might be predictive or foretelling factors concerning drug treatment in patients with this kind of pituitary tumors and also evaluate if there is any response in vitro or in vivo to the treatment with pasireotide in NFPA and resistant prolactinomas and with cabergoline in NFPA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pasireotide | Active Comparator | For non-cured patients with prolactinomas resistant to cabergoline, MRI will be performed immediately before and six months after the onset of pasireotide treatment. The anti-secretory effect will be evaluated by prolactin dosage every month. For patients harboring a NFPA, treatment will be started at least 3 months after neurosurgery, when a pituitary MRI clearly shows the presence of a residual tumor without any possible misinterpretation of postsurgical changes. In this case, the drug efficacy will be evaluated clinically by visual field and by MRI six months after pasireotide treatment. |
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| cabergoline | Active Comparator | In patients with non-functioning pituitary adenoma, treatment will be started at least 3 months after neurosurgery, when a pituitary MRI clearly shows the presence of a residual tumor without any possible misinterpretation of postsurgical changes. The drug response will be evaluated clinically by visual field and by Magnetic resonance imaging (MRI) before medical treatment and after six months of cabergoline treatment at maximum dose. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pasireotide | Drug | The patients with NFPA will be randomized into two groups: (A) the first one will be treated with pasireotide at the dosage of 900 µg s.c. twice a day for 6 months; (B) the second one, with cabergoline 3 mg/week for six months. The patients with resistant prolactinomas will be treated with pasireotide at the dosage of 600 µg s.c. twice a day. After four weeks of treatment, the patients who normalize serum prolactin level will be maintained at the same dosage, the others who do not achieve normal prolactin level will have their dosage raised to 900 µg s.c. twice a day for six months. |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor Volume Changes for NFPA and Prolactin Level Changes for Prolactinoma | Magnetic resonance imaging (MRI) of the sella and prolactin will be performed before (baseline) and after 6 months of treatment with cabergoline or pasireotide. Disease progression will be defined as tumor growth > 25%, stable disease as changes < 25% and significant tumor shrinkage as > 25% in tumor volume compared to baseline MRI (baseline to six months). | Baseline to six months |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Mônica R. Gadelha, PhD | Endocrinology Section - Hospital Universitário Clementino Fraga Filho/Federal University of Rio de Janeiro | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Endocrinology Section - Hospital Universitário Clementino Fraga Filho/Federal University of Rio de Janeiro | Rio de Janeiro | Rio de Janeiro | 21941-913 | Brazil |
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| ID | Title | Description |
|---|---|---|
| FG000 | Pasireotide | Non-cured patients with resistant prolactinomas, MRI will be performed immediately before and six months after the onset of pasireotide. The efficacy will be evaluated by prolactin dosage every month. Patients with a nonfunctioning pituitary adenoma (NFPA), treatment will be started at least 3 months after neurosurgery. The efficacy will be evaluated by MRI 6 months after pasireotide. Pasireotide: The patients with NFPA will be randomized into two groups: (A) the first one will be treated with pasireotide at the dosage of 900 µg s.c. twice a day for 6 months; (B) the second one, with cabergoline 3 mg/week for 6 months. The patients with resistant prolactinomas will be treated with pasireotide at the dosage of 600 µg s.c. twice a day. After 4 weeks of treatment, the patients who normalize serum prolactin level will be maintained at the same dosage, the others who do not achieve normal prolactin level will have their dosage raised to 900 µg s.c. twice a day for 6 months. |
| FG001 | Cabergoline | In patients with non-functioning pituitary adenoma, treatment will be started at least 3 months after neurosurgery. The drug response will be evaluated clinically by visual field and by Magnetic resonance imaging (MRI) before medical treatment and after six months of cabergoline treatment at maximum dose. cabergoline: The patients with NFPA will be randomized into two groups: (A) the first one will be treated with pasireotide at 900 µg s.c. twice a day for 6 months; (B) the second one, with cabergoline 3 mg/week for 6 months. The patients with resistant prolactinomas will be treated with pasireotide at 600 µg s.c. twice a day. After four weeks of treatment, the patients who normalize serum prolactin level will be maintained at the same dosage, the others who do not achieve normal prolactin level will have their dosage raised to 900 µg s.c. twice a day for six months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Pasireotide | For non-cured patients with resistant prolactinomas , MRI will be performed before and six months after the onset of pasireotide. The efficacy will be evaluated by prolactin dosage every month. For patients harboring a NFPA, treatment will be started at least 3 months after neurosurgery. In this case, the drug efficacy will be evaluated clinically by MRI six months after pasireotide. Pasireotide: The patients with NFPA will be randomized into two groups: (A) the first one will be treated with pasireotide at the dosage of 900 µg s.c. twice a day for 6 months; (B) the second one, with cabergoline 3 mg/week for six months. The patients with resistant prolactinomas will be treated with pasireotide at the dosage of 600 µg s.c. twice a day. After four weeks of treatment, the patients who normalize serum prolactin level will be maintained at the same dosage, the others who do not achieve normal prolactin level will have their dosage raised to 900 µg s.c. twice a day for six months. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Tumor Volume Changes for NFPA and Prolactin Level Changes for Prolactinoma | Magnetic resonance imaging (MRI) of the sella and prolactin will be performed before (baseline) and after 6 months of treatment with cabergoline or pasireotide. Disease progression will be defined as tumor growth > 25%, stable disease as changes < 25% and significant tumor shrinkage as > 25% in tumor volume compared to baseline MRI (baseline to six months). | Posted | Median | Full Range | cmˆ3 | Baseline to six 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 | Pasireotide | For non-cured patients with resistant prolactinomas , MRI will be performed immediately before and six months after the onset of pasireotide . The efficacy will be evaluated by prolactin dosage every month. For patients harboring a NFPA, treatment will be started at least 3 months after neurosurgery. In this case, the drug efficacy will be evaluated by MRI six months after pasireotide. Pasireotide: The patients with NFPA will be randomized into two groups: (A) the first one will be treated with pasireotide at the dosage of 900 µg s.c. twice a day for 6 months; (B) the second one, with cabergoline 3 mg/week for six months. The patients with resistant prolactinomas will be treated with pasireotide at the dosage of 600 µg s.c. twice a day. After four weeks of treatment, the patients who normalize serum prolactin level will be maintained at the same dosage, the others who do not achieve normal prolactin level will have their dosage raised to 900 µg s.c. twice a day for six months. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperglycemia | Endocrine disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Monica Gadelha | Universidade Federal do Rio de Janeiro | +552139382323 | mgadelha@hucff.ufrj.br |
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| ID | Term |
|---|---|
| D015175 | Prolactinoma |
| ID | Term |
|---|---|
| D000236 | Adenoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C517782 | pasireotide |
| D000077465 | Cabergoline |
| ID | Term |
|---|---|
| D004873 | Ergolines |
| D004876 | Ergot Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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|
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| cabergoline | Drug | The patients with NFPA will be randomized into two groups: (A) the first one will be treated with pasireotide at 900 µg s.c. twice a day for 6 months; (B) the second one, with cabergoline 3 mg/week for 6 months. The patients with resistant prolactinomas will be treated with pasireotide at 600 µg s.c. twice a day. After four weeks of treatment, the patients who normalize serum prolactin level will be maintained at the same dosage, the others who do not achieve normal prolactin level will have their dosage raised to 900 µg s.c. twice a day for six months. |
|
|
| Adverse Event |
|
| BG001 | Cabergoline | In patients with non-functioning pituitary adenoma, treatment will be started at least 3 months after neurosurgery. The drug response will be evaluated clinically by visual field and by Magnetic resonance imaging (MRI) before medical treatment and after six months of cabergoline treatment at maximum dose. cabergoline: The patients with NFPA will be randomized into two groups: (A) the first one will be treated with pasireotide at 900 µg s.c. twice a day for 6 months; (B) the second one, with cabergoline 3 mg/week for 6 months. The patients with resistant prolactinomas will be treated with pasireotide at 600 µg s.c. twice a day. After four weeks of treatment, the patients who normalize serum prolactin level will be maintained at the same dosage, the others who do not achieve normal prolactin level will have their dosage raised to 900 µg s.c. twice a day for six months. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Cabergoline | In patients with non-functioning pituitary adenoma, treatment will be started at least 3 months after neurosurgery. The drug response will be evaluated clinically by visual field and by Magnetic resonance imaging (MRI) before medical treatment and after six months of cabergoline treatment at maximum dose. cabergoline: The patients with NFPA will be randomized into two groups: (A) the first one will be treated with pasireotide at 900 µg s.c. twice a day for 6 months; (B) the second one, with cabergoline 3 mg/week for 6 months. The patients with resistant prolactinomas will be treated with pasireotide at 600 µg s.c. twice a day. After four weeks of treatment, the patients who normalize serum prolactin level will be maintained at the same dosage, the others who do not achieve normal prolactin level will have their dosage raised to 900 µg s.c. twice a day for six months. |
|
|
|
| 0 |
| 12 |
| 2 |
| 12 |
| EG001 | Cabergoline | In patients with non-functioning pituitary adenoma, treatment will be started at least 3 months after neurosurgery. The drug response will be evaluated clinically by visual field and by Magnetic resonance imaging (MRI) before medical treatment and after six months of cabergoline treatment at maximum dose. cabergoline: The patients with NFPA will be randomized into two groups: (A) the first one will be treated with pasireotide at 900 µg s.c. twice a day for 6 months; (B) the second one, with cabergoline 3 mg/week for 6 months. The patients with resistant prolactinomas will be treated with pasireotide at 600 µg s.c. twice a day. After four weeks of treatment, the patients who normalize serum prolactin level will be maintained at the same dosage, the others who do not achieve normal prolactin level will have their dosage raised to 900 µg s.c. twice a day for six months. | 0 | 9 | 0 | 9 |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D010911 |
| Pituitary Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004700 | Endocrine System Diseases |
| D006576 |
| Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |