Pituitary TumorPhase 2PASSILCORTNCT02749227
Pasireotide LAR Therapy of Silent Corticotroph Pituitary Tumors
A Phase 2 study testing Pasireotide LAR in people with Pituitary Tumor and ACTH-producing Pituitary Tumour, run by Columbia University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pituitary Tumor, ACTH-producing Pituitary Tumour
- What is being tested?
- Pasireotide LAR
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jul 2017to 31 Mar 2020
- Phase
- Phase 2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- 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)
- Plasma POMC level > upper limit of normal
- Prior pituitary tumor surgery with residual or recurrent pituitary tumor visible on MRI scan that is ≥ 5 mm from the optic chiasm.
- Surgical resection of the pituitary adenoma must have occurred two or more months prior to enrollment
- If patients have undergone pituitary radiotherapy they must have completed their course of radiotherapy at least 2 months prior to study screening
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- No prior somatostatin analog therapy
- No concurrent use of dopamine agonist therapy
- No active malignancy
- Stable pituitary hormone supplements (x 2 months) prior to baseline visit
- Sign and date an informed consent document indicating that the subject has been informed of and agrees to all pertinent aspects of the trial
Who cannot join
- Subjects must not meet any of the following exclusion criteria to be eligible for enrollment into the study:
- Patients with Cushing's disease (biochemical evidence of hypercortisolism)
- Patients with compression of the optic chiasm causing any visual field defect that requires surgical intervention
- Diabetic patients with poor glycemic control as evidenced by HbA1c >8%
- Patients who are hypothyroid or adrenally insufficient and not on adequate replacement therapy
- Patients with symptomatic cholelithiasis and acute or chronic pancreatitis
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- Patients with risk factors for torsade de pointes, i.e., patients with a baseline QTcF (Fridericia's Correction Formula value) >450 ms in males, and >460 ms in females
- Hypokalaemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome or concomitant medications with known risk of Torsades de pointes (TdP). Drugs with possible risk of TdP should be avoided whenever feasible
- 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 myocardial infarction (MI) less than one year prior to study entry or clinically significant impairment in cardiovascular function
- Concomitant disease(s) that could prolong the QT interval such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
- Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 2.0 X upper limit of normal (ULN), serum bilirubin >2.0 X ULN
- Presence of Hepatitis B surface antigen (HbsAg) or Hepatitis C antibody test (anti-HCV)
- Patients with serum creatinine >2.0 X ULN
- Patients with white blood cell (WBC) count <3 X 109/L; Hb 90% < lower limit of normal (LLN); platelet (PLT) count <100 X 109/L
- Patients with the presence of active or suspected acute or chronic uncontrolled infection
- Patients who have undergone major surgery/surgical therapy for any cause within 4 weeks prior screening
- Patients with abnormal coagulation (PT and/or activated partial thromboplastin time (APTT) elevated by 30% above normal limits) or patients receiving anticoagulants that affect PT (prothrombin time) or APTT (activated partial thromboplastin time)
- History of syncope or family history of idiopathic sudden death
- History of immunocompromise, including a positive HIV test result (ELISA and Western blot)
- Sexually active males unless they use a condom during intercourse while taking drug and for 3 months following last dose of pasireotide and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and 3 months following last dose of pasireotide. Highly effective contraception methods include:
- Total abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
- Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject
- Combination of any two of the following (a+b or a+c, or b+c):
- Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
- In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
- Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
Trial locations and contacts
1 site in 1 country.
United States1 site
Neuroendocrine Unit and Pituitary Center, Columbia University
New York, New York, 10032
About this study
Official title: Pilot Study of Pasireotide LAR Treatment of Silent Corticotrophin Pituitary Tumors and Effects on Plasma Levels of POMC
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.
Read the 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.
- Conditions
- Pituitary Tumor, ACTH-producing Pituitary Tumour
- Being tested
- Pasireotide LAR
- Keywords
- Clinically non-functioning pituitary adenomas (CNFAs), silent corticotroph adenomas
- Medical subject headings
- Pituitary Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pasireotide LARDrug
Also called Signifor 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.
| Study group | Role | What they receive |
|---|---|---|
| Pasireotide LAR Therapy | Experimental | Subjects will receive Pasireotide LAR monthly. Safety labs and Pituitary MRI will be performed. Receives: Drug: Pasireotide LAR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Plasma Proopiomelanocortin (POMC) Levels
This is to measure the effect of Pasireotide LAR (long-acting release) treatment.
Measured: Baseline, 12 months
Secondary outcomes (1)
Change in Pituitary Tumor Volume
This is to measure the effect of Pasireotide LAR (long-acting release) treatment.
Measured: Baseline, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2016 (estimated)
- Study start10 Jul 2017
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Why it stopped: Lack of funding
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 Pituitary TumorStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pamela U. Freda, Columbia University
- Investigators
- Pamela Freda, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02749227
- Sponsor's protocol ID
- AAAQ6255
- Other IDs
- CSOM230GUS44T
- Acronym
- PASSILCORT
- Status last verified
- Mar 2020
- First submitted
- 20 Apr 2016
- Last updated
- 27 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Pasireotide LAR Treatment of Silent Corticotrophin Pituitary Tumors and Effects on Plasma Levels of POMC
- ClinicalTrials.gov ID
- NCT02749227
- Acronym / sponsor ID
- PASSILCORT / AAAQ6255
- Conditions
- Pituitary Tumor, ACTH-producing Pituitary Tumour
- Keywords
- Clinically non-functioning pituitary adenomas (CNFAs), silent corticotroph adenomas
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 10 Jul 2017 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 22 Apr 2016 (estimated)
- Results
- Posted 27 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pasireotide LAR Therapy | Experimental | Drug: Pasireotide LARSubjects will receive Pasireotide LAR monthly. Safety labs and Pituitary MRI will be performed. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- 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)
- Plasma POMC level > upper limit of normal
- Prior pituitary tumor surgery with residual or recurrent pituitary tumor visible on MRI scan that is ≥ 5 mm from the optic chiasm.
- Surgical resection of the pituitary adenoma must have occurred two or more months prior to enrollment
Key exclusion criteria (31 listed)
- Subjects must not meet any of the following exclusion criteria to be eligible for enrollment into the study:
- Patients with Cushing's disease (biochemical evidence of hypercortisolism)
- Patients with compression of the optic chiasm causing any visual field defect that requires surgical intervention
- Diabetic patients with poor glycemic control as evidenced by HbA1c >8%
- Patients who are hypothyroid or adrenally insufficient and not on adequate replacement therapy
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 |
|---|---|---|
| Pasireotide LARAlso: Signifor LARPasireotide 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. | Drug | Pasireotide LAR Therapy |
Primary outcome
Change in Plasma Proopiomelanocortin (POMC) Levels
Time frame: Baseline, 12 months
This is to measure the effect of Pasireotide LAR (long-acting release) treatment.
1 secondary outcome
Change in Pituitary Tumor Volume
Time frame: Baseline, 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Pamela Freda, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pasireotide LAR in people with Pituitary Tumor and ACTH-producing Pituitary Tumour, run by Columbia University at 1 site in United States.
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 11 inclusion and 31 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: stopped early, as of the sponsor's last update on 27 Apr 2021. 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 United States. 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 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.
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 27 Apr 2021). 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?
Change in Plasma Proopiomelanocortin (POMC) Levels (time frame: Baseline, 12 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 27 Apr 2021.