Triapine + Targeted Radiation for Neuroendocrine Cancer

Recruiting at 17 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Uncontrolled illness, Heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 32 weeks

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding a drug called triapine to the standard treatment, lutetium Lu 177 dotatate, can more effectively shrink or slow the growth of neuroendocrine tumors that have spread. Triapine stops tumor cell growth, while lutetium Lu 177 dotatate delivers radiation directly to tumor cells. People with neuroendocrine tumors that have spread and have not responded to other treatments might be suitable candidates, especially if they have shown disease progression in the last two years. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have recovered from adverse effects of previous treatments to a certain level, and you cannot be on other investigational agents. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that triapine has been tested in patients with various solid tumors. It stops tumor cells from growing by blocking the enzymes needed for DNA production. While some patients have experienced side effects, these are usually manageable.

Lutetium Lu 177 dotatate, on the other hand, has already received FDA approval for treating certain neuroendocrine tumors. Studies have shown that it is generally safe. Common side effects include low levels of lymphocytes (a type of white blood cell crucial for the immune system), increased levels of the liver enzyme GGT, and occasional vomiting.

Overall, both treatments have a well-understood and manageable safety profile in clinical settings. Monitoring for side effects and discussing them with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for neuroendocrine cancer?

Researchers are excited about these treatments because they offer a novel approach for tackling neuroendocrine cancer. Unlike standard treatments such as somatostatin analogs, chemotherapy, or surgery, Triapine combined with Lutetium Lu 177 Dotatate introduces a dual mechanism: Triapine inhibits ribonucleotide reductase, potentially enhancing the cancer-killing effects of Lutetium Lu 177 Dotatate, a targeted radiation therapy. This combination aims to improve the precision and effectiveness of treatment by attacking cancer cells more directly and possibly reducing tumor growth more efficiently. Meanwhile, Lutetium Lu 177 Dotatate on its own is already a cutting-edge treatment, known for its ability to deliver targeted radiation directly to cancer cells, minimizing damage to surrounding healthy tissue. This layered approach could lead to better outcomes and expand treatment options for patients with neuroendocrine tumors.

What evidence suggests that this trial's treatments could be effective for metastatic neuroendocrine tumors?

Studies have shown that Lutetium Lu 177 dotatate, a radioactive drug, effectively treats neuroendocrine tumors. It attaches to specific proteins on tumor cells, delivering radiation directly to them and helping to kill the cancer cells. In this trial, some participants will receive Lutetium Lu 177 dotatate alone, while others will receive it in combination with Triapine. Research suggests that adding Triapine, a drug that inhibits enzymes necessary for cancer cell growth, might enhance the effect of Lutetium Lu 177 dotatate. Triapine has shown promise in lab studies by stopping tumor cell growth. Although more data is needed to fully confirm its effectiveness, combining these treatments could potentially shrink tumors or slow their growth in patients with advanced neuroendocrine tumors. ^{6 7 8 9 10}

Who Is on the Research Team?

Lowell Anthony, MD, FACP

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with well-differentiated, metastatic neuroendocrine tumors that have progressed despite previous treatments can join. They must not have lung NETs, prior peptide receptor radionuclide therapy, or significant uncontrolled conditions. Eligible participants need functioning major organs and controlled hepatitis if present. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

Platelets >= 100,000/mcL

I have recovered from side effects of my previous treatments.

I can take care of myself but may not be able to do heavy physical work.

Exclusion Criteria

I am allergic to medications similar to triapine or lutetium Lu 177 dotatate.

I have recovered from side effects of past treatments, except for hair loss.

Patients with uncontrolled intercurrent illness

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive triapine orally once daily on days 1-14 and lutetium Lu 177 dotatate intravenously on day 1 of each cycle. Cycles repeat every 8 weeks for 4 cycles.

32 weeks

4 visits (in-person) for IV administration, additional visits for imaging and blood collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at 8 and 12 months, then every 6 months for 2 years.

Up to 2 years

Regular follow-up visits every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu 177 Dotatate
• Triapine

Trial Overview The trial is testing the addition of Triapine to Lutetium Lu 177 Dotatate treatment for shrinking or slowing tumor growth in metastatic neuroendocrine tumors compared to using Lutetium Lu 177 Dotatate alone.

How Is the Trial Designed?

Group I: Arm 1 (triapine, lutetium Lu 177 dotatate) Experimental Treatment 5 Interventions

Patients receive triapine PO QD on days 1-14 of each cycle and lutetium Lu 177 dotatate IV over 30 minutes on day 1 of each cycle. Cycles repeat every 8 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.

Group II: Arm 2 (lutetium Lu 177 dotatate) Active Control 4 Interventions

Patients receive lutetium Lu 177 dotatate IV over 30 minutes on day 1 of each cycle. Cycles repeat every 8 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.

Lutetium Lu 177 Dotatate is already approved in European Union, United States for the following indications:

Approved in European Union as Lutathera for:

• Gastroenteropancreatic neuroendocrine tumors

Approved in United States as Lutathera for:

• Gastroenteropancreatic neuroendocrine tumors

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 2 clinical trial involving 37 patients with progressive gastroenteropancreatic neuroendocrine tumors, treatment with Lutetium (177) DOTATATE showed that 28% of patients had a partial response and 41% had stable disease, indicating effective disease control.

The therapy was well tolerated with no significant acute or delayed toxicity observed, and it led to improvements in patients' performance status and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. Delpassand, ES., Samarghandi, A., Zamanian, S., et al.[2022]

Lutetium-177-dotatate (177Lu) therapy for midgut neuroendocrine tumors can be safely administered in an outpatient setting, with a total of 22 patients treated and effective management of radiation exposure during the process.

After implementing changes based on initial experiences, including the use of peripherally inserted central catheters (PICC), the rates of nausea and vomiting significantly decreased in the second cohort of patients, indicating improved patient comfort and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience and lessons learned with implementing Lutetium-177-dotatate radiopharmaceutical therapy in a radiation oncology-based program. Maughan, NM., Kim, H., Hao, Y., et al.[2021]

In a study of 79 patients with progressive neuroendocrine tumors treated with Lu-DOTATATE, 13% showed a partial response and 64% had stable disease, with a median time to progression of 28 months overall.

The treatment was found to be safe, with only a few patients experiencing mild toxicity, including grade 1 haematotoxicity and nephrotoxicity, supporting its use as an effective option for managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. Pencharz, D., Walker, M., Yalchin, M., et al.[2019]

Lutetium Lu-177 dotatate is an effective treatment for gastroenteropancreatic neuroendocrine tumors, significantly improving progression-free survival, as shown in European studies.

In a study of 12 patients, tumor flare reactions were observed in 5 patients, but these reactions can be effectively managed with corticosteroids or other strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu-177 Dotatate Flare Reaction. Salner, AL., Blankenship, B., Dunnack, H., et al.[2022]

Lutetium Lu 177 dotatate (Lutathera®) is an approved targeted therapy specifically for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), offering a new treatment option for this heterogeneous group of tumors.

Patients who are already receiving octreotide long-acting release may be eligible for this second-line therapy, highlighting the importance of personalized treatment plans in managing advanced NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapy: New Radiolabeled Somatostatin Analogs to Treat Gastroenteropancreatic Neuroendocrine Tumors. Boucher, JE., Sommers, R.[2019]

Targeted radiotherapy using 177Lu-DOTATATE showed significant growth delay in neuroblastoma spheroids, particularly in the CHLA-15 and CHLA-20 cell lines, indicating its potential effectiveness against this cancer.

Combining 177Lu-DOTATATE with radiosensitizing drugs like nutlin-3 and topotecan further enhanced the treatment's efficacy, suggesting that these combinations could improve outcomes for high-risk neuroblastoma patients, especially through p53 signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation in vitro of the efficacy of nutlin-3 and topotecan in combination with 177Lu-DOTATATE for the treatment of neuroblastoma. Tesson, M., Vasan, R., Hock, A., et al.[2019]

In a study of 22 patients with carcinoid syndrome, treatment with 177Lu-DOTATATE significantly reduced bowel movement frequency from an average of 6.1 to 4.6 per day and flushing episodes from 4.3 to 2.4 per day, indicating effective symptom relief.

The therapy also led to a notable decrease in urinary 5-hydroxyindolacetic acid excretion in 56% of patients, suggesting that 177Lu-DOTATATE can be a valuable option for managing symptoms in patients not adequately controlled by somatostatin analogs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE for Symptomatic Control of Refractory Carcinoid Syndrome. Zandee, WT., Brabander, T., Blažević, A., et al.[2021]

Using medium-energy general purpose (MEGP) collimators with effective scatter source estimation (ESSE) correction provides the most accurate dosimetry for (177)Lu-DOTATATE treatment in neuroendocrine tumors, with less than 10% difference from the actual activity ratio.

Low-energy collimators can introduce significant artefacts, particularly when using 208 keV energy windows, highlighting the importance of selecting appropriate collimators and correction techniques for accurate patient-specific dosimetry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving quantitative dosimetry in (177)Lu-DOTATATE SPECT by energy window-based scatter corrections. de Nijs, R., Lagerburg, V., Klausen, TL., et al.[2021]

Lutetium-177-dotatate (177 Lu-dotatate) is an FDA-approved treatment for advanced somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs), based on positive results from the NETTER-1 trial.

A case study presented shows that a patient with a grade 3 pancreatic neuroendocrine tumor and a BRCA1 germline mutation experienced a significant response to 177 Lu-dotatate, suggesting its potential efficacy even in more aggressive tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors. Zhu, M., Bassam Sonbol, M., Halfdanarson, T., et al.[2022]

A 60-year-old woman with a metastatic neuroendocrine tumor showed a partial response after 4 cycles and a complete response after 2 additional maintenance cycles of (177)Lu DOTATATE therapy, indicating its efficacy in treating such tumors.

This case suggests that maintenance therapy with (177)Lu DOTATATE could enhance treatment outcomes for patients with neuroendocrine tumors, warranting further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Resolution of Neuroendocrine Tumor Soft Tissue Metastases After 177Lu DOTATATE PRRT Induction and Maintenance Therapy. Makis, W., McCann, K., Buteau, FA., et al.[2019]

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