Peptide Receptor Radiotherapy with 177Lu-DOTATATE for the Treatment of Recurrent, Refractory, or Unresectable Neuroendocrine Tumors, Pheochromocytoma, or Paraganglioma

Inclusion Criteria

• Disease not amenable to standard treatment (nonresectable or disease present after one or more surgeries and/or octreotide acetate [Sandostatin] treatment) or subject has failed existing first line chemotherapy, biologic therapy, targeted agent therapy or radiation therapy
• Participation in Iowa Neuroendocrine Tumor Registry and recommendation by University of Iowa peptide receptor radionuclide therapy (PRRT) tumor board
• A pathologically confirmed (histology or cytology) neuroendocrine tumor (NET), pheochromocytoma (PCC), or paraganglioma (PGL)
• For patients with measurable or evaluable disease: > 50% of lesions must demonstrate gallium Ga 68-DOTATATE (68Ga-DOTATATE) uptake greater than physiologic liver uptake by visual assessment. At least one lesion must be confirmed by conventional imaging (computed tomography [CT] or magnetic resonance imaging [MRI])
• For patients with measurable disease, the target lesion is one that either has never received external beam radiation or has been previously irradiated and has since demonstrated progression
• For patients with no measurable disease (no measurable target lesions), who have evaluable disease (bone disease, metaiodobenzylguanidine [MIBG] positive disease, liver metastases not detectable on MRI or CT), the disease must be seen on 68Ga-DOTATATE positron emission tomography (PET)/CT
• No previous endogenous radiation with 177Lu-DOTATATE/TOC or yttrium-90 (90Y)-DOTATATE/TOC or I-131 metaiodobenzylguanidine (MIBG) within 12 months of most recent treatment
• Age >= 18 months < 20 years at the time of first study drug administration
• Performance status as determined by Karnofsky >= 60 or Lansky play scale >= 60 at the time of study drug administration * NOTE: Neurologic deficits in patients with brain metastases must have been stable for at least 7 days prior to study enrollment
• Completion of validated Pediatric Quality of Life Questionnaire
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days of study drug administration)
• Platelet count >= 75,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days of study drug administration)
• Hemoglobin >= 8 g/dL (within 7 days of study drug administration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) & alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 10 x institutional upper limit of normal for age (within 7 days of study drug administration)
• Total bilirubin < 3 x upper limit of normal (ULN) (within 7 days of study drug administration)
• Blood urea nitrogen (BUN) < 2 x normal (within 7 days of study drug administration)
• Creatinine normal for age (within 7 days of study drug administration)
• Glomerular filtration rate (GFR) only if creatinine > normal for age: nuclear GFR or creatinine clearance (CrCl) >= 80 ml/min/1.73 m^2 (within 7 days of study drug administration)
• Urinalysis no greater than 1+ hematuria or proteinuria (within 7 days of study drug administration)
• The effects of 177Lu-DOTATATE on the developing human fetus are unknown. For this reason and because class C agents are known to be teratogenic, all subjects capable of becoming pregnant must agree to practice a medically acceptable birth control measure (abstinence, birth control pills, intrauterine devices, vaginal diaphragm, vaginal sponge, or condom with spermicidal jelly) throughout the study and for eight months following the end of the last treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Parent’s ability to understand and the willingness to sign a written informed consent document for children < seven (7) years of age. Children >= seven (7) years of age will sign assent along with parental consent or will co-sign consent with parent in accordance with rules of the state in which treatment is received

Exclusion Criteria

• Pregnant women are excluded from this study because 177Lu-DOTATATE is a class C agent with potential teratogenic or abortifacient effects
• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 177Lu-DOTATATE, breastfeeding should be discontinued until 3 months after the last administration of study drug
• Major surgery within 8 weeks of study drug administration
• External beam radiation to both kidneys (scatter doses of < 500 cGy to a single kidney or radiation to < 50% of a single kidney is acceptable)
• Prior PRRT with 90Y-DOTATOC (TATE) or 177Lu-DOTATOC (TATE) or or 131 I-MIBG for this malignancy within 12 months of first study dose
• Another investigational drug within 8 weeks of study drug administration
• Concurrent, malignant disease for which patient is on active therapy
• Another significant medical, psychiatric, or surgical condition which is currently uncontrolled by treatment and which would likely affect the subject's ability to complete this protocol
• Subjects who have received Sandostatin long-acting release (LAR) or long-acting lanreotide in the past 28 days must be appropriately delayed. Subjects may be maintained on short acting octreotide during the time from last injection of long-acting somatostatin analogue until 8-24 hours (hrs) prior to injection of study drug
• Known antibodies to octreotide, lanreotide, or DOTATATE or history of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-DOTATATE
• Uncontrolled illness including, but not limited to ongoing or active infection, uncontrolled diabetes mellitus, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hepatic cirrhosis or severe impairment, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who have received a prior solid organ transplantation are not eligible
• Patients will be excluded if they have a known allergy to any of the drugs used in the study
• Prior Therapy: * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. At least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea) * Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. Short-acting somatostatin analogues may be given up to eight hours prior to infusion of study drug * Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1 * Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. peg-filgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator * Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors) * Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion or boost infusion: >= 84 days after stem cell infusion * Evidence of graft versus host disease (GVHD) * Autologous stem cell infusion including boost infusion: >= 42 days; cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)