Non-functioning Pituitary AdenomasPhase 2/3NCT01620138
Response to Cabergoline and Pasireotide in Non-functioning Pituitary Adenomas and Resistant Prolactinomas
A Phase 2/3 study testing Pasireotide and cabergoline in people with Non-functioning Pituitary Adenomas and Prolactinomas, run by Universidade Federal do Rio de Janeiro at 1 site in Brazil.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-functioning Pituitary Adenomas, Prolactinomas
- What is being tested?
- Pasireotide and cabergoline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteBrazil
- Study dates
- Mar 2010to Jun 2012
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients aged 18 years or greater
- Patients with confirmed diagnosis of NFPA evidenced by: magnetic resonance imaging (MRI) confirmation of pituitary adenoma and No pituitary tumoral hormone hypersecretion
- Patients with no previous medical treatment
- Patients who had been submitted to surgery but not cured. Lack of cure is defined as presence of remnant tumor on MRI at least three months after surgery (without any possible misinterpretation of postsurgical changes)
- Patients with confirmed diagnosis of resistant prolactinoma by lack of prolactin normalization with a tolerated cabergoline dosage during 12 weeks
- Patients who had been submitted to surgery due to resistance to cabergoline and not cured. Lack of cure is defined as lack of serum prolactin normalization or complete removal of tumor load
- Patients who signed the informed consent
Who cannot join
- Previous pituitary radiotherapy
- High risk for transsphenoidal surgery
- Patients with symptomatic cholelithiasis
- Diabetic patients on antidiabetic medications those fasting blood glucose is poorly controlled as evidenced by HbA1C > 8%
- Patients with abnormal coagulation (prothrombin time (PT) or partial thromboplastin time (PTT) elevated by 30% above normal limits);
- Patients receiving anticoagulants that affect PT or PTT
Show all 13Show fewer
- Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, history of acute MI less than one year prior to study entry or clinically significant impairment in cardiovascular function
- Patients with risk factors for torsade de pointes, i.e. patients with a baseline corrected QT interval (QTc) > 480 ms, hypokalemia, family history of long QT syndrome, and concomitant medications known to prolong QT interval
- Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with (alanine aminotransferase) ALT/ (aspartate aminotransferase) AST more than 2 X upper limit of normal (ULN), serum creatinine > 2.0 X ULN, serum bilirubin > 2.0 X ULN, serum albumin < 0.67 X lower limit of normal (LLN)
- Patients with white blood cell (WBC) < 3 X 109/L; Hgb < LLN; Platelet count (PLT) < 100 X 109/L
- Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results in the opinion of the investigator
- Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method for birth control. Female patients must use barrier contraception with condoms. If oral contraception is used, the patient must have been practicing this method for at least two months prior to enrollment and must agree to continue the oral contraceptive throughout the course of the study and for one month after the last dose of study drug. Male patients who are sexually active are required to use condoms during the study and for 1 month afterwards
- Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving pasireotide
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Endocrinology Section - Hospital Universitário Clementino Fraga Filho/Federal University of Rio de Janeiro
Rio de Janeiro, Rio de Janeiro, 21941-913
About this study
Official title: Somatostatin and Dopamine Receptors Expression in Non-functioning Pituitary Adenomas and Resistant Prolactinomas: Correlation With in Vitro and in Vivo Responsiveness to Somatostatin Analogs and Dopamine Agonist
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.
Read the detailed description
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.
- Conditions
- Non-functioning Pituitary Adenomas, Prolactinomas
- Being tested
- Pasireotide, cabergoline
- Keywords
- Non-functioning pituitary adenomas, Prolactinomas, Cabergoline, Pasireotide, somatostatin receptors, Dopamine receptors
- Medical subject headings
- Prolactinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PasireotideDrug
Also called Signifor
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.
cabergolineDrug
Also called Dostinex
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pasireotide |
| 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. Receives: Drug: cabergoline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline to six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2012 (estimated)
- Study startMar 2010
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-functioning Pituitary AdenomasStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universidade Federal do Rio de Janeiro
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Monica Gadelha, Universidade Federal do Rio de Janeiro
- Investigators
- Mônica R. Gadelha, PhD, Principal investigator, Endocrinology Section - Hospital Universitário Clementino Fraga Filho/Federal University of Rio de Janeiro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01620138
- Sponsor's protocol ID
- CSOM230BBR01T
- Status last verified
- Jul 2016
- First submitted
- 18 Sep 2011
- Last updated
- 22 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Somatostatin and Dopamine Receptors Expression in Non-functioning Pituitary Adenomas and Resistant Prolactinomas: Correlation With in Vitro and in Vivo Responsiveness to Somatostatin Analogs and Dopamine Agonist
- ClinicalTrials.gov ID
- NCT01620138
- Acronym / sponsor ID
- CSOM230BBR01T
- Conditions
- Non-functioning Pituitary Adenomas, Prolactinomas
- Keywords
- Non-functioning pituitary adenomas, Prolactinomas, Cabergoline, Pasireotide, somatostatin receptors, Dopamine receptors
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Universidade Federal do Rio de JaneiroUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 15 Jun 2012 (estimated)
- Results
- Posted 16 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pasireotide | Active comparator | Drug: PasireotideFor 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. |
| cabergoline | Active comparator | Drug: cabergolineIn 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female patients aged 18 years or greater
- Patients with confirmed diagnosis of NFPA evidenced by: magnetic resonance imaging (MRI) confirmation of pituitary adenoma and No pituitary tumoral hormone hypersecretion
- Patients with no previous medical treatment
- Patients who had been submitted to surgery but not cured. Lack of cure is defined as presence of remnant tumor on MRI at least three months after surgery (without any possible misinterpretation of postsurgical changes)
- Patients with confirmed diagnosis of resistant prolactinoma by lack of prolactin normalization with a tolerated cabergoline dosage during 12 weeks
Key exclusion criteria (13 listed)
- Previous pituitary radiotherapy
- High risk for transsphenoidal surgery
- Patients with symptomatic cholelithiasis
- Diabetic patients on antidiabetic medications those fasting blood glucose is poorly controlled as evidenced by HbA1C > 8%
- Patients with abnormal coagulation (prothrombin time (PT) or partial thromboplastin time (PTT) elevated by 30% above normal limits);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PasireotideAlso: SigniforThe 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. | Drug | Pasireotide |
| cabergolineAlso: DostinexThe 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. | Drug | cabergoline |
Primary outcome
Tumor Volume Changes for NFPA and Prolactin Level Changes for Prolactinoma
Time frame: Baseline to six months
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mônica R. Gadelha, PhD principal investigator
Endocrinology Section - Hospital Universitário Clementino Fraga Filho/Federal University of Rio de Janeiro
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Pasireotide and cabergoline in people with Non-functioning Pituitary Adenomas and Prolactinomas, run by Universidade Federal do Rio de Janeiro at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor Volume Changes for NFPA and Prolactin Level Changes for Prolactinoma (time frame: Baseline to six months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2016.