Triapine + Radiation Therapy for Neuroendocrine Cancer

Not currently recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Major surgery, Uncontrolled heart failure, others

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

Compensation: Varies

Number of Visits: 7

Duration: 32 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for neuroendocrine tumors by combining triapine and lutetium Lu 177 dotatate. Triapine may stop cancer cell growth, while lutetium Lu 177 dotatate delivers targeted radiation to these cells. The main goal is to determine the optimal dose and identify any side effects of this combination. It suits individuals with neuroendocrine tumors who have tried other treatments without success and show signs of disease progression. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires you to stop taking long-acting somatostatin analogs (like long-acting octreotide) for at least 4 weeks before starting lutetium Lu 177 dotatate, unless you need them to manage carcinoid syndrome.

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

Research has shown that Lutetium Lu 177 dotatate is usually well-tolerated by patients. Most side effects are mild to moderate, such as nausea and tiredness, while serious side effects occur less frequently. Studies have demonstrated that this treatment is generally safe and often used for treating certain types of tumors.

Triapine remains under study to better understand its safety. It works by stopping cancer cells from growing. Although there is less information about its side effects, ongoing research aims to find the best dose and understand any potential risks. Since this trial is in an early phase, it focuses on learning about safety and the right dosage, meaning the treatment is still closely monitored for any adverse effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Triapine combined with Lutetium Lu 177 Dotatate for neuroendocrine cancer because it offers a novel approach by combining a radiopharmaceutical with a ribonucleotide reductase inhibitor. Unlike standard treatments that mainly focus on chemotherapy or surgery, this combination targets cancer cells with radiation directly while disrupting their DNA synthesis, potentially enhancing the effectiveness of radiation therapy. This dual mechanism could offer a more powerful attack on cancer cells, leading to better outcomes for patients with neuroendocrine tumors.

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

Research has shown that lutetium Lu 177 dotatate, one of the treatments in this trial, effectively treats neuroendocrine tumors. Specifically, the NETTER-1 trial found that it helped patients live longer without disease progression and reduced tumor size or stabilized the disease for some patients. Triapine, another treatment option in this trial, blocks enzymes that cancer cells need to grow. Although specific data on triapine's effectiveness for neuroendocrine tumors is limited, it has shown promise in stopping tumor growth in other cancers. This trial aims to combine these treatments to enhance their effectiveness against neuroendocrine tumors. ^{6 7 8 9 10}

Who Is on the Research Team?

Susanne M Arnold

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with well-differentiated neuroendocrine tumors and positive dotatate scans who have failed at least one cancer treatment. They must show disease progression, have measurable disease, be in good physical condition (ECOG 0-2), and meet specific blood criteria. Excluded are those under 18, pregnant or breastfeeding women, recent major surgery patients, individuals unable to absorb oral meds properly, anyone with uncontrolled heart failure or other serious illnesses.

Inclusion Criteria

Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen, in the opinion of the enrolling physician, are eligible for this trial

Leukocytes >= 2,000/mcL

My cancer has spread, is well-differentiated, and had a positive dotatate scan recently.

Exclusion Criteria

Patients who are receiving any other investigational agents

I cannot swallow pills or have a gut condition affecting medication absorption.

I do not have any uncontrolled illnesses like severe infections or heart problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lutetium Lu 177 dotatate IV and triapine orally in cycles of 56 days for up to 4 cycles

32 weeks

4 cycles, each with 1 in-person visit for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu 177 Dotatate
• Triapine

Trial Overview The trial is testing the combination of Triapine and Lutetium Lu 177 Dotatate for treating neuroendocrine tumors. Triapine blocks enzymes needed for tumor growth while Lutetium Lu 177 Dotatate delivers radiation directly to tumor cells. The study aims to find the best dose and assess side effects.

How Is the Trial Designed?

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

Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study.

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 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]

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]

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 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 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]

This study aims to evaluate the efficacy of four additional cycles of Lutathera® compared to two cycles in patients with progressive well-differentiated intestinal neuroendocrine tumors (NET), with a total of 146 patients participating.

The primary goal is to determine if the additional cycles can improve disease control rates over 6 months without increasing safety concerns, potentially leading to new treatment recommendations for extending patient survival and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized, phase II study to assess the schemas of retreatment with Lutathera® in patients with new progression of an intestinal, well-differentiated neuroendocrine tumor (ReLUTH). Deshayes, E., Assenat, E., Meignant, L., 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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK587368/

Neuroendocrine Tumor 177Lutetium-Dotatate Therapy - NCBI Clinical trials, including the landmark NETTER-1 study, have demonstrated significant improvements in progression-free survival, quality of life ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/early/2025/06/05/jnumed.124.269416

Cost-Effectiveness of [177Lu]Lu-DOTATATE for the Treatment ... The NETTER-2 trial found superior median progression-free survival (22.8 mo vs. 8.5 mo) and similar adverse events and quality-of-life measures ...

3. lutathera-hcp.com lutathera-hcp.com/2l-netter-1-efficacy

2L: NETTER-1 | LUTATHERA® (lutetium Lu 177 dotatate) | HCP Median overall survival was 48 months with LUTATHERA plus 30 mg octreotide LAR versus 36.3 months. In the final OS analysis, there was no statistically ...

4. onclive.com onclive.com/view/lutetium-lu-177-dotatate-yields-partial-responses-in-metastatic-bronchopulmonary-neuroendocrine-tumors

Lutetium Lu 177 Dotatate Yields Partial Responses in ... Lutetium Lu 177 dotatate demonstrated antitumor activity in metastatic BP-NETs, with partial responses in 17% of patients and stable disease in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04665739

NCT04665739 | Testing Lutetium Lu 177 Dotatate in ... Lutetium Lu 177 dotatate may be more effective than everolimus in shrinking or stabilizing advanced bronchial neuroendocrine tumors. Detailed Description.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40310018/

Post-marketing Safety Evaluation of Lutathera ( 177 Lu- ... This study aims to conduct a comprehensive analysis of the adverse events (AEs) associated with Lutathera using FDA Adverse Event Reporting System (FAERS) data.

7. lutathera-hcp.com lutathera-hcp.com/2l-netter-1-safety

2L: NETTER-1 Safety | HCP Most adverse reactions seen in the LUTATHERA arm were grade 1/2 · NETTER-1 Laboratory Abnormalities · LUTATHERA has a well-established safety profile ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/208700s031lbl.pdf

LUTATHERA® (lutetium Lu 177 dotatate) injection, for ... The safety data of LUTATHERA with octreotide was evaluated in NETTER-1 [see ... treatment with LUTATHERA consistent with institutional good radiation safety ...

9. jnm.snmjournals.org jnm.snmjournals.org/content/65/5/746

Effectiveness and Safety of Retreatment with 177Lu ... Overall, our findings demonstrate that additional retreatment cycles of 177Lu-DOTATATE are well tolerated and can offer disease-control benefits ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4131

Safety and time to response of [ 177 Lu]Lu-DOTATATE in ... With a median TTR of 5.7 months, most responses to 177 Lu-DOTATATE occurred during scheduled treatment. Overall, the study confirmed the safety profile of 177 ...