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

Status: Active

Description

This phase II trial studies the side effects of lanreotide and to see how well it works in treating patients with pheochromocytoma or paraganglioma that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Lanreotide is a somatostatin analog (a hormone produced by the hypothalamus and some other tissues such as the pancreas and the gastrointestinal tract) that may interfere with tumor growth.

Eligibility Criteria

Inclusion Criteria

  • 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
  • Histologically or cytologically confirmed diagnosis of malignant paraganglioma or pheochromocytoma and either evidence of metastases or unresectability
  • 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
  • Measurable disease defined as that which can be measured in at least one dimension with a minimum size of 10 mm by computed tomography (CT) scan. The patient must also have at least three baseline radiographic studies obtained in the previous twelve 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 twelve 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 or 68Gallium-DOTATATE scan). Either 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 42 days 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)
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
  • Serum amylase < 1.5 x ULN
  • Serum lipase < 1.5 x ULN
  • Serum calcium < 3 mmol/L
  • Serum creatinine < 1.5 x ULN
  • 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 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); 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)
  • 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 (eg. 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)
  • 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, LAR-octreotide, lanreotide or a therapeutic radiolabeled somatostatin analog (PRRT)
  • Any malignancies except: * Basal cell carcinoma of the skin * 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

Locations & Contacts

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Antonio Tito Fojo
Phone: 212-305-6891
Email: atf2116@cumc.columbia.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess the efficacy of lanreotide acetate (lanreotide) given every 4 weeks in patients with advanced or metastatic paraganglioma/ pheochromocytoma.

II. To assess the toxicity and safety of lanreotide in patients with advanced or metastatic paraganglioma/ pheochromocytoma.

III. To document effects of lanreotide on markers of biochemical activity of advanced or metastatic paraganglioma/ pheochromocytoma.

OUTLINE:

Patients receive lanreotide acetate subcutaneously (SC) every 4 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients with no evidence of disease progression after 52 weeks may continue treatment every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center

Principal Investigator
Antonio Tito Fojo

Trial IDs

Primary ID AAA2820
Secondary IDs NCI-2019-05854
Clinicaltrials.gov ID NCT03946527