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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of pasireotide for individuals with prolactinoma, a condition where a benign pituitary tumor causes elevated prolactin levels. It targets those unable to use standard treatments like dopamine agonists due to side effects, resistance, or other medical reasons. Suitable candidates have a prolactinoma that resists or reacts poorly to regular treatment and are not suitable for surgery. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that pasireotide is likely to be safe for humans?

Research has shown that pasireotide has been tested for safety in conditions like acromegaly, a hormonal disorder. Studies involving 491 patients found that high blood sugar levels, or hyperglycemia, are the most common side effect. This side effect occurs more frequently with pasireotide than with similar treatments.

Although pasireotide is generally safe, monitoring blood sugar levels during treatment is important. Age does not significantly affect how the drug works in the body, but limited data exists for individuals over 65. Therefore, while pasireotide is considered safe, regular monitoring remains crucial, especially for older adults. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for prolactinoma, such as dopamine agonists like cabergoline and bromocriptine, pasireotide offers a different approach. Pasireotide is a somatostatin analog, which works by inhibiting the release of certain hormones, including prolactin, thus directly targeting the source of the problem. Researchers are excited about pasireotide because it provides a novel mechanism of action that could be beneficial for patients who do not respond well to existing therapies. Additionally, pasireotide is administered via injection, which may offer a more controlled release compared to oral medications, potentially leading to better management of prolactin levels.

What evidence suggests that pasireotide might be an effective treatment for prolactinoma?

Research has shown that pasireotide can lower hormone levels in conditions like Cushing's disease by blocking certain hormones. In studies on other pituitary-related conditions, such as Cushing's, pasireotide successfully reduced hormone levels to normal for many patients. Although limited data exists on its use for prolactinoma, its success in similar conditions suggests potential effectiveness. In this trial, all participants will receive pasireotide, offering a promising option for those unable to use standard treatments for prolactinoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Eliza Geer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 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

I am a woman who can have children and am using birth control.

Exclusion Criteria

Not euthyroid

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

Pregnant or breastfeeding women

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK349159/

RESULTS - Pasireotide (Signifor) The primary efficacy outcome for Study B2305 was the proportion of patients who achieved a UFC level within the upper limit of the normal range (defined in the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8877616/

Current and Emerging Medical Therapies in Pituitary Tumors Outcome of Cabergoline Treatment in Men with Prolactinoma: Effects of a 24-Month Treatment on Prolactin Levels, Tumor Mass, Recovery of Pituitary Function ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2012/200677Orig1s000ClinPharmR.pdf

200677Orig1s000 - accessdata.fda.gov The primary efficacy endpoint was the proportion of patients who achieved levels of mean urinary-free cortisol (mUFC) ≤ upper limit of normal ( ...

4. go.drugbank.com go.drugbank.com/drugs/DB06663

Pasireotide: Uses, Interactions, Mechanism of Action Pasireotide is a somatostatin analog used in the treatment of Cushing's disease, specifically for those patients whom pituitary surgery is not appropriate.

5. cancer.gov cancer.gov/clinicaltrials/NCI-2024-02117

A Study of Pasireotide in People With Prolactinoma - NCI This phase II trial tests how well pasireotide works in treating patients with prolactinomas who need treatment beyond dopamine agonist therapy.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2014/203255Orig1s000RiskR.pdf

203255Orig1s000 - accessdata.fda.gov 3.1 Clinical Safety. The clinical safety profile for pasireotide LAR is based on safety data collected from 491 patients with acromegaly ...

7. mdpi.com mdpi.com/1424-8247/17/12/1631

Real-Life Data on the Safety of Pasireotide in Acromegaly The aim of this study is to evaluate the real-world evidence on adverse drug reactions (ADRs) reported for PAS in the EudraVigilance database.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02310269

Long Term Safety and Efficacy of Pasireotide s.c. in ... This is a non-interventional, multinational, multi-center post-marketing study, to further document the safety and efficacy of pasireotide s.c. administered ...

9. canjhealthtechnol.ca canjhealthtechnol.ca/index.php/cjht/article/view/SR0859r/2816

View of Pasireotide (Signifor LAR) Pasireotide results in an increased risk of hyperglycemia compared to other SSAs. AcroQoL = Acromegaly Quality of Life Questionnaire; AE = adverse event; CI = ...

10. signiforlar.com signiforlar.com/wp-content/themes/signifor-lar-theme-patient/dist/pdf/signifor-lar-pi.pdf

HIGHLIGHTS OF PRESCRIBING INFORMATION ... Therefore age is not expected to significantly impact circulating levels of pasireotide. Efficacy and safety data on patients older than 65 years are limited [ ...