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

Neuroendocrine Tumors Clinical Trial

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

Status Recruiting

Clinical Trial Summary

Background:

Pheochromocytoma and paraganglioma are rare tumors. They usually form inside and near the adrenal gland or in the neck region. Not all these tumors can be removed with surgery, and there are no good treatments if the disease has spread. Researchers think a new drug may be able to help.

Objective:

To learn the safety and tolerability of Lu-177-DOTATATE. Also, to see if it improves the length of time it takes for the cancer to return.

Eligibility:

Adults who have an inoperable tumor of the study cancer that can be detected with Ga-68-DOTATATE PET/CT imaging

Design:

Participants will be screened with a medical history, physical exam, and blood tests.

Eligible participants will be admitted to the NIH Clinical Center.

Participants will get the study drug in an intravenous infusion. They will get 4 doses, given about 8 weeks apart.

Between 4 and 24 hours after each study drug dose, participants will have scans taken. They will lie on their back on a scanner table.

Participants will have vital signs taken. They will give blood and urine samples.

During the study, participants will have other scans taken. Some scans will use a radioactive tracer.

Participants will complete quality of life questionnaires.

Participants will be contacted by phone 1-3 days after they leave the Clinical Center. They will then be followed every 3 to 6 months for 3 years or until their disease gets worse.

Clinical Trial 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.

• 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. ;

Related Conditions & MeSH terms

• Neuroendocrine Neoplasms
• Neuroendocrine Tumors
• Paraganglioma
• Pheochromocytoma

• NCT number: NCT03206060
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Joy Zou, R.N.
• Phone: (240) 760-6153
• Email: zoujh@mail.nih.gov
• Status: Recruiting
• Phase: Phase 2
• Start date: October 10, 2017
• Completion date: January 1, 2027