Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
Same as current

Summary

Conditions
  • Neuroendocrine Neoplasms
  • Neuroendocrine Tumors
  • Paraganglioma
  • Pheochromocytoma
Type
Interventional
Phase
Phase 2
Design
Allocation: N/AIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

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 extraadrenally are called PGLs. Whil...

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 extraadrenally 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. Patients 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. Simon 2-stage optimal design will be applied to each cohort independently. For each cohort, if 11/18 participants are progression-free at 6 months, accrual will proceed to the second stage, where an additional 23 participants will be accrued, for a total of 41 participants per cohort. Assuming a loss-to-follow-up rate of 10%, a total of 45 participants will be accrued to each cohort, with a total accrual ceiling of 90 participants.

Tracking Information

NCT #
NCT03206060
Collaborators
Not Provided
Investigators
Principal Investigator: Frank I Lin, M.D. National Cancer Institute (NCI)