A Study of Pasireotide in People With Prolactinoma
This phase II trial tests how well pasireotide works in treating patients with prolactinomas who need treatment beyond dopamine agonist therapy. Prolactinoma causes your body to make too much of a hormone called prolactin, and this increase in prolactin can cause a decrease in sex hormones (for example, estrogen and testosterone). Additionally, the patient's tumor has not responded to or cannot receive dopamine agonist therapy. Dopamine agonists are drugs that stop the patient's body from making too much prolactin and can shrink prolactinomas. Pasireotide is a drug that attaches to somatostatin receptors (SSTRs), which are proteins that play a role in inhibiting (decreasing) hormones, including prolactin. After attaching to SSTRs, pasireotide works to decrease prolactin production. Giving pasireotide may kill more tumor cells in patients with prolactinomas who need treatment beyond dopamine agonist therapy.
Inclusion Criteria
- Age 18 or older
- Male and female patients with prolactinomas with at least one of the following criteria: * Clinical intolerance due to adverse events on dopamine antagonist (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.
- 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).
- 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.
- At least 8 weeks washout of prior first-generation somatostatin receptor ligand therapy (octreotide or lanreotide).
- Patients on temozolomide will need a washout period of at least 3 weeks.
- Patients on carboplatin, cisplatin or etoposide will need a washout period of at least 4 weeks.
- 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.
- In general, at least 4 weeks must have elapsed from any other anticancer drug therapy (e.g., bevacizumab).
- 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.
- White blood cell (WBC) ≥ 2000/uL
- Neutrophils ≥ 1500/uL
- Platelets ≥ 100 x 10^3/uL
- Hemoglobin > 9.0 g/dL
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x upper limit normal (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
- Karnofsky performance status (KPS) 70 or above
- Measurable tumor by RECIST v1.1 criteria, ≥ 10 mm.
- 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.
- 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
- Additional pituitary tumor directed therapy, including temozolomide, everolimus, lapatinib, or cytotoxic chemotherapy
- Concurrent malignancy except non-melanoma skin cancer
- Any pituitary surgery within 14 days of enrollment.
- Patients with poorly controlled diabetes as defined by HBA1c > 9% or not optimally treated for diabetes mellitus as judged by the investigator
- Patients who are not euthyroid as judged by the investigator
- 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
- Patients with QTc > 500 ms
- History of intolerance or resistance to pasireotide
- Women who are pregnant or breast-feeding
- Inability to undergo radiographic surveillance
- Inability to provide informed consent
Additional locations may be listed on ClinicalTrials.gov for NCT06295952.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Middletown
Montvale
New York
Commack
New York
Uniondale
West Harrison
PRIMARY OBJECTIVE:
I. To assess the biochemical 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, as per prior trial data, of pasireotide LAR treatment in patients with prolactinomas who have failed dopamine agonist therapy.
SECONDARY OBJECTIVES:
I. To assess the radiographic response to pasireotide LAR treatment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version (v)1.1 (30% decrease in longest tumor diameter) within 24 weeks of pasireotide treatment.
II. To evaluate the biochemical response rate as defined by a decrease in serum prolactin concentration by ≥ 50% within week 24.
III. To characterize safety of pasireotide LAR defined by adverse events included in package insert (including fasting plasma glucose level, change in glycated haemoglobin [HBA1c]%, change in serum aspartate aminotransferase [AST] and alanine transaminase [ALT], and change in corrected QT (QTc) from baseline to 24 weeks).
EXPLORATORY OBJECTIVES:
I. Quantify SSTR5 expression (defined by percent of cells with positive SSTR5 expression) by immunohistochemistry (IHC) on archival tumors with available pathology (i.e., from those patients who have undergone prior pituitary surgery, which will be a sub-group of the cohort).
II. Quantify the baseline 68Ga-DOTATOC tumor uptake, defined by Krenning scale.
III. Descriptively and graphically assess pre-treatment 68Ga-DOTATOC tumor uptake and response to pasireotide treatment.
OUTLINE:
Patients receive pasireotide intramuscularly (IM) every 4 weeks (Q4W) on day 1 of each cycle. Treatment repeats every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. At week 25, patients may optionally enter extension phase and continue to receive pasireotide and monitoring per standard of care (SOC). Patients also receive Ga 68-DOTATATE intravenously (IV) then undergo positron emission tomography (PET)/computed tomography (CT) during screening, undergo ultrasound during screening and as clinically indicated on study, and magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up at 30 days.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorEliza Geer
- Primary ID23-371
- Secondary IDsNCI-2024-02117
- ClinicalTrials.gov IDNCT06295952