Study to Evaluate the Safety of Combining Two Radionuclide Therapies to Treat Mid-gut Neuroendocrine Tumors

• Status: Active, not recruiting
• Trial end date: 2027-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: David Bushnell
• Collaborators: Holden Comprehensive Cancer Center; National Cancer Institute (NCI); National Institutes of Health (NIH)
• Treatments: Edotreotide; Octreotide

Criteria

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)