Pasireotide for Prolactinoma

Recruiting at 6 trial locations

Overseen By Andrew Lin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Dopamine agonists

Must not be taking: Temozolomide, Everolimus, Lapatinib, others

Disqualifiers: Concurrent malignancy, Diabetes, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The researchers are doing this study to find out whether pasireotide is an effective treatment for people with prolactinoma who cannot receive dopamine agonist therapy. Another purpose of this study is to find out whether pasireotide is a safe treatment for people with prolactinoma.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some treatments. If you are on first-generation somatostatin receptor ligand therapy, temozolomide, carboplatin, cisplatin, etoposide, or protein kinase inhibitors, you will need to stop these medications for a specified time before joining the trial. However, if you are on dopamine agonist therapy like cabergoline or bromocriptine, you may continue at a stable or lower dose.

What data supports the effectiveness of the drug Pasireotide for treating prolactinoma?

Pasireotide has been shown to be effective in treating conditions like Cushing's disease and acromegaly, which involve similar hormone-secreting tumors, suggesting it might also help with prolactinoma. It works by targeting multiple somatostatin receptors, potentially making it more effective than other treatments that target fewer receptors. ^{1 2 3 4 5}

How is the drug pasireotide unique for treating prolactinoma?

Pasireotide is unique because it is a somatostatin analog that binds to multiple somatostatin receptor subtypes, potentially making it more effective than other treatments that target fewer receptor types. It is also used in conditions like Cushing's disease and acromegaly, where it has shown efficacy, although it may affect glucose metabolism. ^{1 2 3 4 6}

Research Team

Eliza Geer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with prolactinoma who can't take dopamine agonist therapy, aren't candidates for surgery, and meet specific health criteria. They must not have other cancers (except non-melanoma skin cancer), be pregnant or breastfeeding, have had recent pituitary surgery, poorly controlled diabetes, liver disease, or a prolonged QTc interval.

Inclusion Criteria

I am 18 years old or older.

I have a prolactin-producing tumor and cannot tolerate or respond to standard treatments.

Screening laboratory values meeting specific criteria including WBC, neutrophils, platelets, hemoglobin, liver function tests, renal function, performance status, and tumor size

Exclusion Criteria

Not euthyroid

I have no cancer other than non-melanoma skin cancer.

Pregnant or breastfeeding women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pasireotide LAR, starting at 40 mg IM, with potential increase to 60 mg IM every 4 weeks if tolerated

24 weeks

6 visits (in-person, every 4 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pasireotide

Trial Overview The study tests the effectiveness and safety of Pasireotide in treating prolactinoma among patients intolerant to standard treatment. It aims to see if this drug can manage tumor-related high prolactin levels without causing significant harm.

Participant Groups

Group I: Pasireotide Experimental Treatment 2 Interventions

All patients will initiate open-label treatment with pasireotide LAR on week 1 in the outpatient setting. Pasireotide will be initiated at 40 mg IM one time dose and if tolerated dose will be increased to 60 mg IM every 4 weeks +/-7 days. Administration of pasireotide will align with package inset. Patients must return to the study center every 28 days (+/- 7 days) to receive study medication and for evaluation.

Pasireotide is already approved in United States, European Union for the following indications:

Approved in United States as Signifor for:

• Cushing's disease

Approved in European Union as Signifor for:

• Cushing's disease

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Recordati Pharmaceutical company

Collaborator

Trials

2

Recruited

230+

Evergreen Theragnostics

Collaborator

Trials

1

Recruited

10+

RECORDATI GROUP

Industry Sponsor

Trials

13

Recruited

4,500+

Findings from Research

In a study involving 45 healthy male volunteers, pasireotide treatment led to significant reductions in insulin secretion during glucose tolerance tests, indicating a mechanism for the hyperglycemia associated with this medication.

The hyperglycemia observed with pasireotide is linked to decreased responses of incretin hormones, rather than changes in insulin sensitivity, suggesting that the drug affects insulin production rather than how the body uses insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. Henry, RR., Ciaraldi, TP., Armstrong, D., et al.[2022]

Pasireotide is effective in treating Cushing's disease and acromegaly, providing biochemical control and tumor volume reduction, with a similar safety profile to first-generation somatostatin analogues, although it has a higher incidence of hyperglycemia.

This drug may also be beneficial as a second-line therapy for metastatic neuroendocrine tumors and in preventing postoperative complications after pancreatectomy, highlighting its potential versatility in treating various conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pasireotide - Mechanism of Action and Clinical Applications. Sawicka-Gutaj, N., Owecki, M., Ruchala, M.[2018]

Pasireotide is rapidly absorbed in the body, reaching peak plasma concentration within 0.5 hours after a single subcutaneous dose, indicating efficient absorption.

The drug is primarily excreted unchanged, with about 84% of the dose eliminated in its original form, mostly through feces, and no serious adverse events were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the absorption, metabolism and excretion of [¹⁴C]pasireotide in healthy volunteers using accelerator mass spectrometry. Lin, TH., Hu, K., Flarakos, J., et al.[2014]

In a phase II study involving 60 patients with acromegaly, pasireotide demonstrated a higher biochemical response rate (27%) after 3 months compared to octreotide (9%) after 4 weeks, indicating its potential effectiveness in reducing growth hormone levels.

Pasireotide was generally well tolerated, and 39% of patients experienced a significant reduction in pituitary tumor volume, suggesting it may also help shrink tumors associated with acromegaly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial. Petersenn, S., Schopohl, J., Barkan, A., et al.[2014]

In a study involving 8 MEN1 transgenic mice with insulinoma, treatment with the somatostatin analogue SOM230 significantly reduced serum insulin levels and increased serum glucose levels, indicating its antisecretory effects.

SOM230 also demonstrated antiproliferative effects by reducing tumor size and promoting apoptosis in tumor cells, suggesting its potential as a therapeutic option for patients with insulinoma associated with MEN1 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pasireotide (SOM230) is effective for the treatment of pancreatic neuroendocrine tumors (PNETs) in a multiple endocrine neoplasia type 1 (MEN1) conditional knockout mouse model. Quinn, TJ., Yuan, Z., Adem, A., et al.[2021]

Pasireotide long-acting release (LAR) formulation was well tolerated in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP NET), with 81% of participants reporting adverse events, primarily mild symptoms like diarrhea and fatigue.

The study achieved steady-state plasma levels of pasireotide after three monthly injections, indicating effective drug delivery and potential for sustained therapeutic effects in patients refractory to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a long-acting release (LAR) formulation of pasireotide (SOM230) in patients with gastroenteropancreatic neuroendocrine tumors: results from a randomized, multicenter, open-label, phase I study. Wolin, EM., Hu, K., Hughes, G., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Pasireotide - Mechanism of Action and Clinical Applications. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

Assessment of the absorption, metabolism and excretion of [¹⁴C]pasireotide in healthy volunteers using accelerator mass spectrometry. [2014]

4. United States pubmed.ncbi.nlm.nih.gov

Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial. [2014]

5. United States pubmed.ncbi.nlm.nih.gov

Pasireotide (SOM230) is effective for the treatment of pancreatic neuroendocrine tumors (PNETs) in a multiple endocrine neoplasia type 1 (MEN1) conditional knockout mouse model. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a long-acting release (LAR) formulation of pasireotide (SOM230) in patients with gastroenteropancreatic neuroendocrine tumors: results from a randomized, multicenter, open-label, phase I study. [2022]