Background - Pheochromocytomas/paragangliomas (PHEOs/PGLs) are rare tumors arising from neural crest tissue that can develop in sympathetic and parasympathetic paraganglia throughout the body. Those arising in the adrenal gland are called PHEOs while those located extra-adrenally are called PGLs. While benign and uni-focal, PHEO/PGL can be effectively treated with surgical resection, patients with metastatic PHEO/PGL often times have few effective and efficient treatment options with current treatments aimed more at palliation and symptom control. Furthermore, some benign head and neck PGLs may be inoperable because of their size and location. Somatostatin receptors (SSTR), especially type 2, have been shown to be over-expressed in a number of human tumors, including gastroenteropancreatic (GEP), carcinoids, neuroblastoma, prostate cancer, and PHEO/PGL among many others. Ionizing radiation such as the beta particles emitted by Lu-177 cause DNA damage to target cells through both direct and indirect mechanisms. In addition, ionizing radiation has also been shown to induce cell death through what is known as the bystander effect, a phenomenon where cellular signaling from irradiated cells towards non-irradiated cells induces cellular damage and eventually death in nearby surrounding cells. Lu-177-DOTATATE is a somatostatin analog that predominantly recognizes SSTR2. This reagent has been used extensively and its well-tolerated safety profile and efficacy has been shown in a variety of neuroendocrine tumors. Primary Objective: To assess the safety and to evaluate the ability of Lu-177-DOTATATE to improve upon progression-free survival (PFS) at 6 months in patients with inoperable, SSTR positive PHEO/PGL by comparing PFS of patients treated with Lu-177-DOTATATE to historical controls from existing literature. Eligibility: Histologically-proven, surgically inoperable, PHEO/PGL patients (both newly diagnosed or patients with existing diagnoses are eligible). Must have presence of SSTR+ disease as documented by positive Ga-68-DOTATATE PET scan o Positivity of Ga-68-DOTATATE PET scan defined as having at least one lesion that is 10 mm in diameter with uptake that is higher than or equal to liver and is qualitatively higher and distinguishable from background activity. Patients with bone-only disease (i.e. no RECIST-measurable lesion) will also be eligible as long as the Ga-68-DOTATATE PET scan is positive - Age: 18 - Karnofsky Performance Score 60. Able to understand and willing to sign informed consent. Design: Open-label, single-arm, single-center, phase 2 study evaluating efficacy and safety of Lu-177-DOTATATE in the selected patient population divided into two cohorts: 1) SDHx cohort will include patients with the succinate dehydrogenase mutation, which is the most common and most aggressive genetic sub-group of patients with PHEO/PGL, and 2) apparent sporadic cohort which will include patients without a clear genetic mutation. Simon 2-stage optimal design will be applied to each cohort independently. For each cohort, if 11/18 patients are progression-free at 6 months, accrual will proceed to the second stage, where an additional 23 patients will be accrued, for a total of 41 patients per cohort. Assuming a loss-to-follow-up rate of 10%, a total of 45 patients will be accrued to each cohort, with a total accrual ceiling of 90 patients.
