A Clinical Trial Evaluating the Safety of Combining Lutathera(R) and Azedra(R) to Treat Mid-gut Neuroendocrine Tumors — SPORE-3  

Neuroendocrine Tumors Clinical Trial

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

Status Withdrawn

Clinical Trial Summary

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.

Clinical Trial Description

Azedra and Lutatheraare are FDA-approved radioactive drugs designed to treat specific tumor cells. These drugs are a combination of the radiation (131-Iodine, 177-lutetium) and a protein that targets the tumor cell (MIBG or DOTATATE). Because these proteins are attracted to, and stick to, the tumor, the radiation is centered in the tumors. This kills more tumor cells and minimizes radiation-damage to healthy tissues, like the heart and lungs.

Two organs still absorb some of the radiation, though: bone marrow and the kidney. These organs limit how much radiation can be given to tumors, but we don't know how much radiation is too much. Too much radiation to bone marrow can result in anemia. Too much radiation to the kidneys can result in kidney failure. From prior radiation therapies, we have a general idea of how much radiation we can give safely.

Azedra and Lutathera have never been given together. We want to give them together because many times, tumors are actually groups of different types of cells. This means, not all the cells respond to therapy the same way. If some tumor cells survive therapy, the tumor will continue to grow and eventually come back. We know some mid-gut neuroendocrine tumors (NETs) have targets for DOTATATE and some other mid-gut NETs have targets for MIBG. We also have now identified that some people with mid-gut NETs have different tumors: some with targets for MIBG and some with targets for DOTATATE. For these people, this means treating only with Azedra or Lutathera will not be enough to treat their cancer. They need both radioactive drugs.

Because we are combining these radioactive drugs, this study is known as a first-in-man study. We are also using a special imaging to help us estimate the radiation dose to the bone marrow and to the kidneys. This is what decides the final dose of Azedra and Lutathera.

After receiving a standard treatment of Lutathera, participants are asked to undergo imaging to verify they have both MIBG and DOTATATE tumor types:

• participants are given a tracer dose of Azedra

• a special camera (SPECT/CT) collects images (scans)

• imaging (scans) are done over 4 calendar days

• blood samples are taken at that time, too, to measure the circulating amount of tracer doses

If the scans show a participant does not have both MIBG and DOTATATE receptors, they continue with standard therapy (Lutathera only). Participants are asked to still undergo study assessments to provide a comparison group.

If the scans show a participant has both MIBG and DOTATATE receptors, combined therapy is administered:

• a customized dose of Lutathera is given on day 1 of a treatment cycle. This is given outpatient.

• a customized dose of Azedra is given on day 2 of a treatment cycle. This is given inpatient (admitted to the hospital).

• participants are monitored through blood tests to identify the side effects of therapy.

Each participant can have up to 2 cycles of therapy. The cycles are 12 weeks apart.

The doses for Lutathera and Azedra are decided based on radiation to the bone marrow and radiation to the kidney. Doses are decided by how well other participants have done on this study.

Participants have life long follow-up for this study. This is very important, because a study like this has not been done. ;

Related Conditions & MeSH terms

• Gastro-enteropancreatic Neuroendocrine Tumor
• Neoplasms
• Neuroendocrine Tumors

• NCT number: NCT04614766
• Study type: Interventional
• Source: University of Iowa
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: September 30, 2022
• Completion date: April 23, 2024