Lanreotide for the Treatment of Metastatic or Unresectable Pheochromocytoma or Paraganglioma, the LAMPARA Study

Inclusion Criteria

• Male or female at least 18 years of age at the time of first dosing
• Patients must give signed informed consent before any study-related activities are conducted
• Patients in the United States must have given written authorization for the release of protected health information in compliance with Health Insurance Portability and Accountability Act (HIPAA) regulations; patients in other countries must provide appropriate authorization as needed by regulatory authorities in each country
• Histological or cytological confirmation of malignant paraganglioma or pheochromocytoma with either evidence of metastases or unresectability. In the case of glomus jugulare and carotid body tumors, their clinical presentation and demonstration of avidity on a gallium DOTATATE scan are sufficient
• Evidence of recent disease progression (radiological, biochemical, symptomatic) while the patient was either not receiving any therapy or was receiving a therapy that was deemed ineffective. Note: Radiographic progression need not adhere to a Response Evaluation Criteria in Solid Tumors (RECIST) definition of progression * NOTE: Paragangliomas can arise in the jugular fossa / jugular foramen of the temporal bone (glomus jugulare tumors) and in the carotid body (with acronyms that include carotid body tumor, glomus tumor, chemodectomas, and nonchromaffin tumor that are less accurate or obsolete). They arise from glomus cells located within the outermost wall of the jugular bulb or from paraganglionic cells of the carotid body which contains neural elements originating from the neural crest ectoderm. Often considered benign as they may not present with metastases, they often present enormous clinical challenges since they can be locally very aggressive and difficult if not impossible to resect. Given their critical location such tumors are almost never biopsied. However, their unique clinical presentation together with avidity on somatostatin-receptor scintigraphy (gallium DOTATATE scan) are considered diagnostic. Furthermore, as they often grow very slowly, the magnitude of change in size may be small, but provided the pre-requisite baseline scans are available, these patients will be eligible to enroll on study. As such, patients who present with glomus jugulare or carotid body tumors will be eligible for enrollment on study based on the clinical/scintigraphic presentation without tissue confirmation. Additionally, patients with tumors secreting catecholamines in whom sites of potential biopsy are felt to present a risk, may be enrolled without a confirmatory biopsy after consultation with the Principal Investigator, provided their clinical presentation together with avidity on somatostatin-receptor scintigraphy (gallium DOTATATE scan) are considered diagnostic
• Measurable disease defined as that which can be measured in at least one dimension with a minimum size of 10 mm by an appropriate imaging study including magnetic resonance imaging (MRI), computed tomography (CT) scan or another appropriate imaging modality. The patient must also have at least three baseline radiographic studies obtained in the previous eighteen months with at least one scan obtained within six weeks of enrollment. If a patient being considered for enrollment on trial has not had three scans performed in the eighteen months prior to enrollment and if in the opinion of the investigator a delay of one month will not impact the clinical course, then enrollment on protocol and the start of the lanreotide therapy can be delayed by one month or longer to obtain the additional time point. If in the opinion of the investigator such a delay may have adverse consequences then enrollment on the protocol should not be considered as an option
• Confirmation of positive somatostatin receptor status by somatostatin receptor scintigraphy (SRS, octreotide/pentetreotide scan, 68Gallium-DOTATATE scan, or copper [CU]64 DOTATATE scan). Any of these studies will need to have been performed in the 6 months prior to the Screening Visit. Only if one has not been performed within the previous 6 months will a SRS study be required
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Life expectancy of greater than 12 weeks
• Patients must have prothrombin time (PT)/ international normalized ratio (INR)/ partial thromboplastin time (PTT) within 2 x the upper limit
• Patients may have had prior radiation therapy. A minimum of 2 weeks must have elapsed between the end of radiotherapy and registration onto the study. Measurable disease must exist outside of the radiation field for eligibility
• Previous major surgery is permitted provided that it was performed at least 28 days prior to patient registration
• Absolute granulocyte count (AGC) > 1.5 x 10^9/L
• Platelet count > 100 x 10^9/L
• Serum bilirubin < 1.5 x upper limit of normal (ULN) or < 2.5 x ULN if liver metastases
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
• Serum calcium < 3 mmol/L
• Glomerular filtration rate > 30 ml/min/1.73m^2
• If female, the patient must not be pregnant (confirmed by negative pregnancy test) and must have the following documented via verbally given history: * At least 1 year postmenopausal (natural cessation of menses), or * Surgically sterile (if by tubal ligation, surgery must have been performed more than 3 months prior to entry into the study), or * If the female patient is of childbearing potential and sexually active, she must be using or agree to use an acceptable form of contraception (oral, injected, transdermal or implanted contraceptives, diaphragm or barrier method with spermicidal and/or intrauterine device) throughout the duration of the study up until 6 months after the last dose; local methods such as condoms or sponges/vaginal tablets are only to be used as an additional form of contraception
• If the male patient has a partner of childbearing potential and he is sexually active, he must be using or agree to use a barrier method of contraception (condom with spermicidal preferred) and agree to not donate sperm throughout the duration of the study up until 6 months after the last dose
• Be able to communicate and cooperate with the principal investigator and the staff and willing to comply with the study instructions

Exclusion Criteria

• Patient has a history of known allergy or hypersensitivity to: * Investigational drug or any components of its formulation * Lanreotide, octreotide or any other somatostatin analog
• Treatment with any other investigational drug or with “cytotoxic chemotherapy” within 28 days prior to the start of study therapy (lanreotide) and/or at any time during the patient’s participation in the study
• Treatment with sunitinib, radiotherapy, a radiolabeled somatostatin receptor (SSTR) analog, and/or tumor debulking < 14 days prior to the start of study therapy (lanreotide). Treatment with metaiodobenzylguanidine (MIBG) therapy < 90 days prior to the start of study therapy (lanreotide)
• History of hepatic arterial embolization or hepatic arterial chemoembolization < 28 days prior to the start of study therapy (lanreotide). Measurable disease shall exist outside of treated lesions for eligibility
• History of hepatic selective internal radiation therapy (e.g. Sir-spheres) < 90 days prior the start of study therapy (lanreotide). Measurable disease shall exist outside the liver for eligibility
• Uncontrolled diabetes (defined as inability to maintain fasting blood glucose levels below 200 mg/dL despite best medical therapy, within last 28 days prior to screening) and/or hypertension (defined as inability to maintain blood pressure levels below systolic 140 mmHg and/or diastolic 90 mm Hg on at least three antihypertensive medications, within last 28 days prior to screening)
• Unstable hypertension defined as a systolic blood pressure > 170 mmHg or diastolic pressure > 105 mmHg despite optimal medical management on three successive measurements at least 4 hours apart
• Renal impairment (glomerular filtration rate < 30 ml/min/1.73m^2) and/or liver impairment (serum total bilirubin > 1.5 x ULN, or > 2.5 x ULN if liver metastases)
• Uncontrolled cardiac disease (acute myocardial infarction, unstable angina or hospitalization for decompensation of congestive heart failure within the 28 days prior to the start of study therapy (lanreotide)
• Patients may not have had prior octreotide, long-acting release (LAR)-octreotide, landreotide or a therapeutic radiolabeled somatostatin analog (peptide receptor radionuclide therapy [PRRT]) within the last 3 years
• Any malignancies except: * Basal cell carcinoma of the skin or other non-melanoma skin malignancy that has been successfully resected * In situ carcinoma of the cervix * 2 years disease-free after curative cancer treatment (completion of surgery, adjuvant chemotherapy and/or radiation, and considered no evidence of disease from non PPGL malignancy)
• Any serious medical condition that could jeopardize the safety of the patient and/or the efficacy assessments of the study