Phase 1 Trial Using 131I MIBG and 90Y DOTATOC in a Dosimetrically Determined Optimal Combination for Therapy of Selected Patients With Midgut Neuroendocrine Tumors.

201608857

This study is designed to identify the best tolerated doses of \[131\]Iodine-MIBG and \[90\]Yttrium-DOTATOC when co-administered to treat midgut neuroendocrine tumors. These drugs (131I-MIBG, 90Y-DOTATOC) are radioactive drugs, known as radionuclide therapy. Currently, the safest and best tolerated doses of these drugs (when combined together) is unknown.

2017-05-07

2025-12-01

2027-12-01

Active (not recruiting)

Early phase I

20

A 2-step eligibility is utilized for this study. STEP 1: Inclusion Criteria: * Ability to understand and the willingness to provide informed consent. * A pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2). The primary tumor location should be known or believed to be midgut, or pheochromocytoma, or paraganglioma. * Disease not amenable to curative intent treatment (primarily surgery) and in addition has shown either clinical or radiographic progression on all available (non-radionuclidic) therapies known to confer clinical benefit. * SSTR positive sites as demonstrated by either SSTR2 positivity (2+ or 3+ intensity and greater than 10% tumor cell occupying the receptors) or a nuclear medicine scan utilizing 111In-DTPA-Phe3-Octreotide (Octreoscan™) or 68Ga-DOTA-tyr3-Octreotide within 12 months prior to anticipated C1D1 demonstrating SSTR positive tumor sites * ≥1 tumor site must have demonstrated uptake equal to or greater than normal liver as documented by nuclear scan imaging * ≥1 evaluable site of disease measuring ≥ 1.5 cm in diameter on CT or MRI as measured per RECIST * ≥ 18 to 70 years at the time of study drug administration. * Karnofsky Performance Status at least 70% * Agrees to contraception. Exclusion criteria: * Patients who are considered a fall risk. * Women who are pregnant or breast feeding. * Surgery, radiation or chemotherapy within 4 weeks of proposed step 1 start date. * Prior peptide-receptor radiotherapy (PRRT). * Investigational drug within 4 weeks of proposed step 1 start date. * More than one concurrent, malignant disease. * History of congestive heart failure and cardiac ejection fraction ≤ 40%. * Patients for whom, in the opinion of their physician, a 24-hour discontinuation of somatostatin analogue therapy represents a health risk. * Patients who are unable to discontinue medications known to affect MIBG uptake * Proteinuria, grade 2 (i.e., ≥ 2+proteinuria). * Long-acting somatostatin analogue treatment within 14 days of proposed step 1 start date. * Prior external beam radiation involving kidneys (scatter doses of \< 500 cGy to a single kidney or radiation to \< 50% of a single kidney is acceptable). * Prior external beam radiation (including brachytherapy) involving 25% of bone marrow (excluding scatter doses of ≤ 5 Gy). * History of allergic reactions attributed to compounds of similar chemical or biologic composition to 90Y-DOTA-tyr3-Octreotide, Octreoscan®, 68Ga-Octreotide, or 131I-MIBG. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. If a subject meets STEP 1 criteria, a serial SPECT scan is performed for dosimetry. Step 2 criteria must be met and verified prior to therapy initiation. STEP 2: Inclusion Criteria: * Subjects must demonstrate at least one of the following: * One or more MIBG+ and DOTATOC- tumors in addition to one or more DOTATOC+ tumors, and/or, * One or more tumor sites where the calculated "safe" radiation tumor dose is higher by at least 25% with a combination of 131I-MIBG and 90Y-DOTATOC than it is with 90Y DOTATOC alone, or, * Within 2 weeks of study drug administration for therapeutic intent, patients must have normal organ and marrow function as defined below: * absolute neutrophil count ≥ 2000 cells/mm3 * platelets ≥100,000 cells/mm3 * total bilirubin \<1.5 x institutional ULN for age and weight * AST(SGOT) ≤ 2.5 x institutional ULN * ALT (SGPT) ≤ 2.5 x institutional ULN * eGFR ≥ 50 mL/min/1.73 m2 (Cockroft Gault formula)

{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'dose-escalation design', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ESTIMATED'}}

2023-08-16