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.
12345What 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.
12678Is 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.
126910Eligibility 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.
+19 more
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
+5 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm 1 (triapine, lutetium Lu 177 dotatate)Experimental Treatment5 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 Control4 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Pittsburgh Cancer Institute (UPCI)Pittsburgh, PA
NYP/Weill Cornell Medical CenterNew York, NY
University of Wisconsin Carbone Cancer Center - University HospitalMadison, WI
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareIrvine, CA
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Lutetium Lu-177 Dotatate Flare Reaction. [2022]Lutetium Lu-177 dotatate is the first peptide receptor radionuclide therapy approved by the US Food and Drug Administration. Well-designed studies in Europe have shown dramatic effectiveness in improving progression-free survival in patients with gastroenteropancreatic neuroendocrine tumors, which are progressive and generally metastatic. This therapy is a molecular targeted therapy linking a beta-emitting radioisotope to dotatate, which binds tightly to somatostatin receptors on neuroendocrine tumors cells. Various adverse effects of this therapy have been reported in the literature, including potential toxicity to renal, hepatic, and hematologic tissues and risk of second malignancy. Our study sought to explore acute adverse effects in this patient population.
Initial experience and lessons learned with implementing Lutetium-177-dotatate radiopharmaceutical therapy in a radiation oncology-based program. [2021]Label="PURPOSE">To assist radiation oncology centers in implementing Lutetium-177-dotatate (177Lu) radiopharmaceutical therapy for midgut neuroendocrine tumors. Here we describe our workflow and how it was revised based on our initial experience on an expanded access protocol (EAP).
Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE for Symptomatic Control of Refractory Carcinoid Syndrome. [2021]Peptide receptor radionuclide therapy (PRRT) with [Lutetium-177-DOTA0-Tyr3]octreotate (177Lu-DOTATATE) results in an increase of progression-free survival and quality of life in patients with progressive, well-differentiated neuroendocrine neoplasms (NENs).
Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors. [2022]Lutetium-177-dotatate (177 Lu-dotatate), a form of peptide receptor radionuclide therapy, was approved by the U.S. Food and Drug Administration for the treatment of advanced somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs) in 2018 based on the promising results of the NETTER-1 trial for grade 1-2 midgut NETs. Here, we present a patient with a grade 3 pancreatic neuroendocrine tumor and BRCA1 germline mutation who had a significant response to 177 Lu-dotatate.
Complete Resolution of Neuroendocrine Tumor Soft Tissue Metastases After 177Lu DOTATATE PRRT Induction and Maintenance Therapy. [2019]A 60-year-old woman diagnosed with a well-differentiated neuroendocrine tumor metastatic to the liver and lymph nodes was treated with 4 induction cycles and 2 maintenance cycles of (177)Lu [DOTA,(0)Tyr(3)]octreotate (DOTATATE) peptide receptor radionuclide therapy. Her posttreatment imaging showed partial response after 4 induction cycles and complete response after 2 additional maintenance cycles. This case highlights the need for further research into maintenance (177)Lu DOTATATE therapy to improve outcomes in neuroendocrine tumor patients.
Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]Lutetium-177 DOTA-D-Phe1-Tyr3-octreotide (Lu-DOTATATE) is a treatment option for patients with well-differentiated metastatic neuroendocrine tumours. Our centre started administering this therapy in 2012. The aim of this study was therefore to analyse the first cohort of patients treated with Lu-DOTATATE to determine its early efficacy and toxicity.
Improving quantitative dosimetry in (177)Lu-DOTATATE SPECT by energy window-based scatter corrections. [2021]Patient-specific dosimetry of lutetium-177 ((177)Lu)-DOTATATE treatment in neuroendocrine tumours is important, because uptake differs across patients. Single photon emission computer tomography (SPECT)-based dosimetry requires a conversion factor between the obtained counts and the activity, which depends on the collimator type, the utilized energy windows and the applied scatter correction techniques. In this study, energy window subtraction-based scatter correction methods are compared experimentally and quantitatively.
Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. [2022]Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs is a novel method of treatment in patients with metastatic neuroendocrine tumors (NETs). For the first time in the United States, we present preliminary results of the treatment with Lutetium (177)(Lu) DOTATATE in patients with progressive NETs.
An evaluation in vitro of the efficacy of nutlin-3 and topotecan in combination with 177Lu-DOTATATE for the treatment of neuroblastoma. [2019]Targeted radiotherapy of metastatic neuroblastoma using the somatostatin receptor (SSTR)-targeted octreotide analogue DOTATATE radiolabelled with lutetium-177 (177Lu-DOTATATE) is a promising strategy. This study evaluates whether its effectiveness may be enhanced by combination with radiosensitising drugs. The growth rate of multicellular tumour spheroids, derived from the neuroblastoma cell lines SK-N-BE(2c), CHLA-15 and CHLA-20, was evaluated following treatment with 177Lu-DOTATATE, nutlin-3 and topotecan alone or in combination. Immunoblotting, immunostaining and flow cytometric analyses were used to determine activation of p53 signalling and cell death. Exposure to 177Lu-DOTATATE resulted in a significant growth delay in CHLA-15 and CHLA-20 spheroids, but not in SK-N-BE(2c) spheroids. Nutlin-3 enhanced the spheroid growth delay induced by topotecan in CHLA-15 and CHLA-20 spheroids, but not in SK-N-BE(2c) spheroids. Importantly, the combination of nutlin-3 with topotecan enhanced the spheroid growth delay induced by X-irradiation or by exposure to 177Lu-DOTATATE. The efficacy of the combination treatments was p53-dependent. These results indicate that targeted radiotherapy of high risk neuroblastoma with 177Lu-DOTATATE may be improved by combination with the radiosensitising drugs nutlin-3 and topotecan.
Targeted Therapy: New Radiolabeled Somatostatin Analogs to Treat Gastroenteropancreatic Neuroendocrine Tumors. [2019]Neuroendocrine tumors (NETs), including gastroenteropancreatic NETs, or GEP-NETs, are heterogenous tumors that arise from diffuse neuroendocrine cells and other organs, such as the lung, ovary, and thyroid. Lutetium Lu 177 dotatate (Lutathera®) is a newly approved targeted therapy for patients with advanced GEP-NETs. Patients treated with octreotide long-acting release may be candidates for this second-line therapy. This article discusses lutetium Lu 177 dotatate therapy administration and patient care considerations.