Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma

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, participants 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 participants with inoperable, SSTR positive PHEO/PGL by comparing PFS of participants treated with Lu-177-DOTATATE to historical controls from existing literature. Eligibility: * Histologically-proven, surgically inoperable, PHEO/PGL participants (both newly diagnosed or participants with existing diagnoses are eligible) * Must have presence of SSTR+ disease as documented by positive Ga-68-DOTATATE PET scan * Positivity of Ga-68-DOTATATE PET scan defined as having at least one lesion that is greater than or equal to 10 mm in diameter with uptake that is higher than or equal to liver and is qualitatively higher and distinguishable from background activity. * Measurable disease as defined by RECIST 1.1 * Age: greater than or equal to 18 * Karnofsky Performance Score greater than or equal to 60 or, ECOG Performance Status of 2 or better * Able to understand and willing to sign informed consent Design: * Open-label, single-arm, multi-center, phase 2 study evaluating efficacy and safety of Lu- 177-DOTATATE in the selected participant population divided into two cohorts: 1) SDHx cohort will include participants with the succinate dehydrogenase mutation, which is the most common and most aggressive genetic sub-group of participants with PHEO/PGL, and 2) "apparent sporadic" cohort which will include participants without a clear genetic mutation. * Lu-177-DOTATATE is administered IV every 8 (+/- 2) weeks, for a total of 4 administrations. Gamma whole-body planar and/or SPECT/CT imaging of Lu-177-DOTATATE will be obtained at 4 to 72-hours post-injection to confirm localization of treatment to intended targets (optional for participating sites). A CT/MRI for RECIST, Ga-68-DOTATATE and F-18-FDG PETs will be obtained post-2 administrations and post-4 administrations. * All participants will be contacted by phone within a week after each Lu-177-DOTATATE and in-person every 4 weeks. After the end of treatment visit at week 32, participant will continue to be followed every 12 weeks until 3 years after the first Lu-177-DOTATATE administration. Follow-up visits may be conducted remotely or via telemedicine. After the 3 years, all participants will be contacted yearly until death to assess survival and disease status. * Participants who have met the primary endpoint of having achieved a PFS of at least 6 months after the initial treatment course, may be eligible to receive further cycles of Lu-177-DOTATATE at the time of progression.