Radionuclide Therapies for Neuroendocrine Tumors

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: David Bushnell

Must not be taking: Somatostatin analogues

Disqualifiers: Pregnancy, Congestive heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 16

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications known to affect MIBG uptake and long-acting somatostatin analogues at least 14 days before starting the study. If your doctor thinks stopping somatostatin analogue therapy for 24 hours is risky for you, you may not be eligible to participate.

Is radionuclide therapy with 131I-MIBG and 90Y-DOTATOC safe for treating neuroendocrine tumors?

Radionuclide therapy with 131I-MIBG and 90Y-DOTATOC has been used to treat neuroendocrine tumors, and while it can be effective, it may cause side effects like thrombocytopenia (low platelet count) and granulocytopenia (low white blood cell count). Serious side effects are uncommon, and most patients experience symptom improvement. ^{1 2 3 4 5}

What makes the treatment with 131I-MIBG and 90Y-DOTA-3-Tyr-Octreotide unique for neuroendocrine tumors?

This treatment is unique because it combines two radiopharmaceuticals that target neuroendocrine tumors through different mechanisms: 131I-MIBG targets cells using the amine transporter system, while 90Y-DOTA-3-Tyr-Octreotide binds to somatostatin receptors. This dual approach may enhance the delivery of radiation to tumor cells, potentially improving treatment outcomes. ^{1 3 4 6 7}

What evidence supports the effectiveness of the treatment 131I-MIBG for neuroendocrine tumors?

The treatment 131I-MIBG has shown effectiveness in treating neuroendocrine tumors, with studies indicating it can lead to tumor regression or stabilization and symptomatic improvement in many patients. It has been particularly effective in patients with pheochromocytoma, and when combined with other treatments like 90Y-DOTATOC, it may enhance the radiation dose delivered to tumors, potentially improving outcomes. ^{1 2 3 4 8}

Who Is on the Research Team?

David Bushnell, MD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with midgut neuroendocrine tumors that can't be surgically removed and have worsened despite treatment. They must have certain levels of blood cells, liver function, kidney function, and a tumor visible on scans. Pregnant or breastfeeding women, those at fall risk, with heart failure or other serious health issues are excluded.

Inclusion Criteria

ALT (SGPT) ≤ 2.5 x institutional ULN

To participate, you need to meet at least one of the following requirements:

absolute neutrophil count ≥ 2000 cells/mm3

Exclusion Criteria

I have had radiation that affected my kidneys, but it was limited.

I have not taken long-acting somatostatin analogues in the last 14 days.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

3 visits (in-person)

Imaging and Dosimetry

Participants undergo imaging to verify tumor types and dosimetry to estimate radiation dose

1 week

3 visits (in-person)

Treatment Cycle 1

Participants receive a customized dose of 90Y-DOTATOC and 131I-MIBG over two days

2 days

2 visits (1 outpatient, 1 inpatient)

Treatment Cycle 2

Participants may receive a second cycle of treatment 12 weeks after the first cycle

2 days

2 visits (1 outpatient, 1 inpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Regular visits every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• 131I-MIBG
• 90Y-DOTA-3-Tyr-Octreotide

Trial Overview The study tests combining two radioactive drugs (131I-MIBG and 90Y-DOTATOC) to find the safest doses for treating midgut neuroendocrine tumors. These therapies target tumor cells with radiation from within the body.

How Is the Trial Designed?

Group I: Cohort 3.2 (bone marrow alternative) Experimental Treatment 2 Interventions

This treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 2. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 150 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy) No further dose evaluations are done after this cohort is completed.

Group II: Cohort 3.1 (renal alternative) Experimental Treatment 2 Interventions

This treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 3. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 250 centiGray (cGy) Radiation exposure to the kidneys is limited to 1900 centiGray (cGy) No further dose evaluations are done after this cohort is completed.

Group III: Cohort 3 Experimental Treatment 2 Interventions

This treatment arm is opened if Cohort 2 is successful. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 250 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy)

Group IV: Cohort 2.2 (bone marrow alternative) Experimental Treatment 2 Interventions

This treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 2. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 100 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy) No further dose evaluations are done after this cohort is completed.

Group V: Cohort 2.1 (renal alternative) Experimental Treatment 2 Interventions

This treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 2. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 200 centiGray (cGy) Radiation exposure to the kidneys is limited to 1500 centiGray (cGy) No further dose evaluations are done after this cohort is completed.

Group VI: Cohort 2 Experimental Treatment 2 Interventions

This treatment arm is opened if Cohort 1 is successful. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 200 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy)

Group VII: Cohort 1 Experimental Treatment 2 Interventions

This is the initial treatment arm. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 150 centiGray (cGy) Radiation exposure to the kidneys is limited to 1900 centiGray (cGy)

Group VIII: Cohort -1 (alternative cohort) Experimental Treatment 2 Interventions

This treatment arm is opened if Cohort 1 is not tolerated. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 100 centiGray (cGy) Radiation exposure to the kidneys is limited to 1500 centiGray (cGy) No further dose evaluations are done after this cohort is completed.

131I-MIBG is already approved in United States, European Union for the following indications:

Approved in United States as Azedra for:

• Pheochromocytoma
• Neuroblastoma

Approved in European Union as Iobenguane I-131 for:

• Neuroblastoma
• Pheochromocytoma
• Paraganglioma

Who Is Running the Clinical Trial?

David Bushnell

Lead Sponsor

Trials

4

Recruited

50+

Holden Comprehensive Cancer Center

Collaborator

Trials

27

Recruited

710+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Therapy of neuroendocrine tumors with radiolabeled MIBG and somatostatin analogues. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment of metastatic carcinoid tumors with radiolabeled biologic molecules. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Long-term efficacy of low activity meta-[131I]iodobenzylguanidine therapy in patients with disseminated neuroendocrine tumours depends on initial response. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Feasibility and advantage of adding (131)I-MIBG to (90)Y-DOTATOC for treatment of patients with advanced stage neuroendocrine tumors. [2020]

5. England pubmed.ncbi.nlm.nih.gov

The value of radiolabelled MIBG and octreotide in the diagnosis and management of neuroendocrine tumours. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Long-term outcome and toxicity after dose-intensified treatment with 131I-MIBG for advanced metastatic carcinoid tumors. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Lutetium-177 DOTATATE: A Practical Review. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

¹¹¹In-DTPA⁰-octreotide (Octreoscan), ¹³¹I-MIBG and other agents for radionuclide therapy of NETs. [2015]