Response to Cabergoline and Pasireotide in Non-functioning Pituitary Adenomas and Resistant Prolactinomas

• ClinicalTrials.gov Identifier: NCT01620138
• Recruitment Status: Completed
• First Posted: June 15, 2012
• Results First Posted: June 16, 2016
• Last Update Posted: August 22, 2016
• Sponsor: Universidade Federal do Rio de Janeiro
• Information provided by (Responsible Party): Monica Gadelha, Universidade Federal do Rio de Janeiro

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Non-functioning Pituitary Adenomas; Prolactinomas
• Interventions: Drug: Pasireotide; Drug: cabergoline
• Enrollment: 21

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Pasireotide	Cabergoline
Arm/Group Description	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.	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.
Period Title: Overall Study
Started	12	9
Completed	6	9
Not Completed	6	0
Reason Not Completed
Withdrawal by Subject	3	0
Lack of Efficacy	1	0
Adverse Event	2	0

Baseline Characteristics

Arm/Group Title		Pasireotide	Cabergoline	Total
Arm/Group Description		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.	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.	Total of all reporting groups
Overall Number of Baseline Participants		12	9	21
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	12 participants	9 participants	21 participants
		33; (24 to 63)	54; (36 to 65)	54; (24 to 65)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	9 participants	21 participants
	Female	8 66.7%	5 55.6%	13 61.9%
	Male	4 33.3%	4 44.4%	8 38.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Brazil	Number Analyzed	12 participants	9 participants	21 participants
		12	9	21

Outcome Measures

1. Primary Outcome

Title	Tumor Volume Changes for NFPA and Prolactin Level Changes for Prolactinoma
Description	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).
Time Frame	Baseline to six months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide	Cabergoline
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	6	9
Median (Full Range); Unit of Measure: cmˆ3
	3.8; (3.46 to 4.58)	29.35; (2.55 to 51.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide, Cabergoline
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Pasireotide		Cabergoline
Arm/Group Description	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.		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.
All-Cause Mortality
	Pasireotide		Cabergoline
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Pasireotide		Cabergoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0.00%)		0/9 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pasireotide		Cabergoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.67%)		0/9 (0.00%)
Endocrine disorders
Hyperglycemia † 1	1/12 (8.33%)	1	0/9 (0.00%)	0
Gastrointestinal disorders
Diarrhea † 1	1/12 (8.33%)	1	0/9 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE (4.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Monica Gadelha
• Organization: Universidade Federal do Rio de Janeiro
• Phone: +552139382323
• EMail: mgadelha@hucff.ufrj.br

• Responsible Party: Monica Gadelha, Universidade Federal do Rio de Janeiro
• ClinicalTrials.gov Identifier: NCT01620138
• Other Study ID Numbers: CSOM230BBR01T
• First Submitted: September 18, 2011
• First Posted: June 15, 2012
• Results First Submitted: June 1, 2015
• Results First Posted: June 16, 2016
• Last Update Posted: August 22, 2016