Triapine + Targeted Radiation for Neuroendocrine Cancer

Recruiting at 26 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

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

Trial Summary

What is the purpose of this trial?

This phase II trial compares the effect of adding triapine to lutetium Lu 177 dotatate versus lutetium Lu 177 dotatate alone (standard therapy) in shrinking tumors or slowing tumor growth in patients with neuroendocrine tumors that have spread from where they first started (primary site) to other places in the body (metastatic). Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for deoxyribonucleic acid synthesis and cell growth. Lutetium Lu 177 dotatate is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177 dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Giving triapine in combination with lutetium Lu 177 dotatate may be more effective at shrinking tumors or slowing tumor growth in patients with metastatic neuroendocrine tumors than the standard therapy of lutetium Lu 177 dotatate alone.

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.

What data supports the idea that Triapine + Targeted Radiation for Neuroendocrine Cancer is an effective treatment?

The available research shows that Lutetium Lu-177 dotatate, a part of the Triapine + Targeted Radiation treatment, is effective for neuroendocrine cancer. Studies in Europe have demonstrated that it significantly improves the time patients live without the cancer getting worse. Additionally, it has been shown to improve the quality of life for patients with certain types of neuroendocrine tumors. In one case, a patient experienced a complete resolution of tumor spread after undergoing this treatment. This suggests that the treatment can be very effective, although it may have some side effects. ^{1 2 3 4 5}

What safety data is available for Triapine and Lutetium Lu 177 Dotatate treatment in neuroendocrine cancer?

Lutetium Lu 177 Dotatate, also known as Lutathera, has been studied extensively for its use in treating neuroendocrine tumors. It is a peptide receptor radionuclide therapy that targets somatostatin receptors on tumor cells. Safety data indicates potential adverse effects, including toxicity to renal, hepatic, and hematologic tissues, and a risk of second malignancy. Studies have focused on early efficacy and toxicity, with some reporting acute adverse effects. However, specific safety data for the combination of Triapine with Lutetium Lu 177 Dotatate is not detailed in the provided research. ^{1 2 6 7 8}

Is Triapine a promising drug for neuroendocrine cancer?

Triapine, also known as Lutetium Lu 177 Dotatate, is a promising drug for treating neuroendocrine cancer. It has shown effectiveness in improving survival in patients with certain types of neuroendocrine tumors by targeting specific receptors on cancer cells. This targeted approach helps slow down the progression of the disease. ^{1 2 6 9 10}

Research Team

Lowell Anthony, MD, FACP

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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-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 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]

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]

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]

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]

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]

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]

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]

References

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

Lutetium Lu-177 Dotatate Flare Reaction. [2022]

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

Initial experience and lessons learned with implementing Lutetium-177-dotatate radiopharmaceutical therapy in a radiation oncology-based program. [2021]

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

Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE for Symptomatic Control of Refractory Carcinoid Syndrome. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors. [2022]

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

Complete Resolution of Neuroendocrine Tumor Soft Tissue Metastases After 177Lu DOTATATE PRRT Induction and Maintenance Therapy. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Improving quantitative dosimetry in (177)Lu-DOTATATE SPECT by energy window-based scatter corrections. [2021]

8. United States 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. [2022]

9. United States 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. [2019]

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

Targeted Therapy: New Radiolabeled Somatostatin Analogs to Treat Gastroenteropancreatic Neuroendocrine Tumors. [2019]