A Study of Pasireotide in People With Prolactinoma

Prolactin-Producing Pituitary Tumor Clinical Trial

Official title:

Pasireotide Treatment for Patients With Prolactinomas Who Need Treatment Beyond Dopamine Agonist Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06295952
• Other study ID #: 23-371
• Status: Recruiting
• Phase: Phase 2
• Start date: February 27, 2024
• Est. completion date: February 2027

Study information

• Verified date: April 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Eliza Geer, MD
• Phone: 646-608-3797
• Email: geere[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: February 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age 18 or older

2. Male and female patients with prolactinomas and hyperprolactinemia with at least one

of the following criteria:

• Clinical intolerance due to adverse events on DA treatment, preventing continued treatment.
• Contraindication to DA treatment (e.g., patients requiring dopamine antagonist therapy or other therapy that is contraindicated).
• Tumor resistance to DA, defined as <50% decrease in longest diameter, or progression in tumor size and/or lack of prolactin normalization with at least 2 mg per week, or maximally tolerated dose, of cabergoline or bromocriptine. Patients with a partial response to DA, including a prolactin reduction but not normalization on treatment, will be included, and will continue DA during the study.

3. Patients are not considered candidates for surgery (e.g., poor surgical candidates, inoperable tumors, patients who refuse surgical treatment, or for whom surgery is deemed not appropriate treatment).

4. For patients with a history of pituitary radiation, the following criteria must be

present:

• At least 6 months must have elapsed from the time of the most recent radiation treatment to the time of enrollment, and
• Stable or up trending serum prolactin levels and/or evidence of tumor growth since completion of radiation.

5. At least 8 weeks washout of prior first-generation somatostatin receptor ligand therapy (octreotide or lanreotide).

6. Patients on temozolomide will need a washout period of at least 3 weeks.

7. Patients on carboplatin, cisplatin or etoposide will need a washout period of at least 4 weeks.

8. Patients on protein kinase inhibitors (e.g., everolimus, lapatinib) will need a washout period of at least 5 half-lives or 2 weeks, whichever in longer.

9. In general, at least 4 weeks must have elapsed from any other anticancer drug therapy (e.g., bevacizumab).

10. Stable or lower dose of DA (cabergoline or bromocriptine) for at least one month for those patients continuing DA treatment, i.e. DA dose may not be escalated during trial enrollment.

11. Screening laboratory values must meet the following criteria:

• WBC = 2000/µL
• Neutrophils = 1500/µL
• Platelets = 100 x103/µL
• Hemoglobin > 9.0 g/dL
• AST/ALT = 3 x ULN
• Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
• Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 40 mL/min using the Cockcroft-Gault formula

12. Karnofsky Performance Status (KPS) 70 or above

13. Measurable tumor by RECIST V1.1 criteria, = 10 mm.

14. Women of childbearing potential (WOCBP) must use appropriate methods of contraception while participating in the trial until 30 days after the follow-up period.

• WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. Women who are not of childbearing potential are not required to use contraception.
• Women of childbearing potential must have a negative serum or urine pregnancy test upon study entry.

15. Men who are sexually active with women of childbearing potential must use adequate contraception while participating in the trial. Men who are surgically sterile or azoospermia do not require contraception.

Exclusion Criteria:

1. Additional pituitary tumor directed therapy, including temozolomide, everolimus, lapatinib, or cytotoxic chemotherapy

2. Concurrent malignancy except non-melanoma skin cancer

3. Any pituitary surgery within 14 days of enrollment.

4. Patients with poorly controlled diabetes as defined by HBA1c >9% or not optimally treated for diabetes mellitus as judged by the investigator

5. Patients who are not euthyroid as judged by the investigator

6. Patient with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with serum ALT and/or AST >3x ULN, or total bilirubin >1.5 x ULN

7. Patients with QTc > 500 ms

8. History of intolerance or resistance to pasireotide

9. Women who are pregnant or breast-feeding

10. Inability to undergo radiographic surveillance

11. Inability to provide informed consent

Related Conditions & MeSH terms

• Pituitary Neoplasms
• Prolactin-Producing Pituitary Tumor
• Prolactinoma

Intervention

Drug:
• Pasireotide
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.

Other:
• SF-36 and HADS
Baseline assessment will be conducted within 30 days of starting treatment, week 12, 24 and week 28.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (3)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Evergreen Theragnostics, Recordati Pharmaceutical company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	biochemical response rate	response rate as defined by a normal serum prolactin concentration (<18.0 ng/ml for a male and < 29.0 ng/ml for a female	within 24 weeks of treatment
Secondary	radiographic response	RECIST criteria, V1.1 (30% decrease in longest tumor diameter)	within 24 weeks of treatment

External Links

•   Memorial Sloan Kettering Cancer Center