Triapine + Radiation Therapy for Neuroendocrine Cancer

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

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of triapine when given together with lutetium Lu 177 dotatate in treating patients with neuroendocrine tumors. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and not harm normal cells. Giving triapine and lutetium Lu 177 dotatate together may work better to treat patients with neuroendocrine tumors.

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.

What data supports the effectiveness of the treatment Triapine + Radiation Therapy for Neuroendocrine Cancer?

Research shows that Lutetium Lu-177 dotatate, a component of the treatment, has been effective in improving progression-free survival in patients with gastroenteropancreatic neuroendocrine tumors, and there are cases of complete resolution of tumor metastases after its use. ^{1 2 3 4 5}

Is the combination of Triapine and Lutetium Lu 177 Dotatate safe for humans?

Lutetium Lu 177 Dotatate has been used in treating neuroendocrine tumors and has shown some adverse effects, including potential damage to the kidneys, liver, and blood cells, as well as a risk of developing another cancer. Safety measures are necessary to protect patients and healthcare workers from radiation exposure during treatment. ^{1 3 5 6 7}

How is the Triapine + Radiation Therapy treatment for neuroendocrine cancer different from other treatments?

This treatment combines Triapine, a drug that inhibits cancer cell growth, with Lutetium Lu 177 Dotatate, a targeted therapy that delivers radiation directly to tumor cells, making it unique by using both a chemical and a radiopharmaceutical approach to target neuroendocrine tumors. ^{1 3 5 6 8}

Research Team

Susanne M Arnold

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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 (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]

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]

References

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

Lutetium Lu-177 Dotatate Flare Reaction. [2022]

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

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

3. 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]

4. 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]

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

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

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

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

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

Occupational and ambient radiation exposures from Lu-177 DOTATATE during targeted therapy. [2021]

8. England 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). [2022]