A Phase 1/2 Trial Using AZEDRA and LUTATHERA in a Dosimetrically-determined Optimal Combination for Therapy of Selected Patients With Midgut Neuroendocrine Tumors

202005556

This study is designed to identify the best tolerated doses of Lutathera® and Azedra® when co-administered to treat midgut neuroendocrine tumors. These drugs are radioactive drugs, known as radionuclide therapy, and are both approved in the treatment of midgut neuroendocrine tumor as single agents (not together). Currently, the safest and best tolerated doses of these drugs (when combined) is unknown. That is the purpose of this clinical trial.

2022-09-30

2024-04-23

2024-04-23

Withdrawn

Early phase I

Inclusion Criteria: * Ability to understand and willingness to provide informed consent; legally authorized representative will not be utilized compliant with the principles of good clinical practice (i.e., ICH E6(R2)). * Stated willingness to comply with all study procedures and availability for duration of study * Aged ≥ 18 years to 80 years at the time of study drug administration * Pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be: * a well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2) with a primary tumor location believed to be midgut, or, * pheochromocytoma, or, * paraganglioma * Recommended to receive LUTATHERA® or AZEDRA® therapy * Disease measuring ≥ 1.5 cm in diameter on CT or MRI as measured per RECIST * Adequate performance status (ECOG of 0 or 1; or KPS of \>70). * Agrees to contraception during therapy. * Agreement to adhere to Lifestyle Considerations throughout study duration Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: * Patient with increased fall risk in the opinion of healthcare professionals * Women who are pregnant. * Women who are breast feeding. * Surgery, radiation therapy, or chemotherapy ≤ 4 weeks of C1D1. (Toxicities from prior therapies should have resolved to ≤ CTCAE grade 1 or a new baseline established). * Prior peptide-receptor radiotherapy (PRRT). * Therapeutic investigational drug within 4 weeks of C1D1 (imaging agents are acceptable). * A concurrent malignancy that, in the opinion of the investigator, would cause a safety risk by delaying therapy or confound/negatively impact study objectives (documentation of the rationale must be provided). * History of congestive heart failure with a history of cardiac ejection fraction ≤ 35%. * Patients unable to discontinue medications known to affect MIBG uptake (unless approved by the PI or designee) * Proteinuria grade 2 (i.e., 2+ proteinuria). * Prior external beam radiation dose of \>16 Gy to the kidneys. * Prior external beam radiation (including brachytherapy) involving 25% of the bone marrow (excluding scatter doses of 5 Gy) as estimated by a radiation oncologist. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Octreoscan® or Netspot™. Participants meeting the above criteria will receive one cycle of standard Lutathera treatment (200 millicuries) as well as a tracer dose of Azedra for imaging. Participants will then undergo protocol specific imaging to calculate the radiation dose to the kidneys, the bone marrow, and to the tumor lesions. To continue on study and receive the combined therapy, a participant's imaging must demonstrate one of the following: * At least one tumor that is positive for Azedra but negative for Lutathera in addition to Lutathera positive tumors, or, * At least one tumor site where the calculated safe radiation dose to that tumor site is 25% higher using the combined therapy compared to Lutathera alone Participants who do not meet this criteria are invited to participate in the comparator arm to receive standard Lutathera treatment as indicated by their physicians.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants who do not meet eligibility criteria for the combined therapy will be asked to participate in the active comparator, which is single agent Lutathera administered as per FDA guidelines.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 0, 'type': 'ACTUAL'}}

2024-04-29