Lutathera for Neuroendocrine Tumors

(NETTER-P Trial)

Not currently recruiting at 12 trial locations

Overseen By Novartis Pharmaceuticals

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Advanced Accelerator Applications

Disqualifiers: Pregnancy, Breastfeeding, Other malignancies, 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: 4

Duration: 32 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Lutathera, a treatment for young patients with specific types of neuroendocrine tumors. The goal is to assess the safety and effectiveness of this treatment for tumors that cannot be surgically removed. Eligible participants are adolescents with advanced tumors expressing certain receptors, confirmed through imaging tests. The study aims to provide insights into treating these challenging conditions in young patients. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that Lutathera is likely to be safe for humans?

Research has shown that Lutathera, a treatment for certain neuroendocrine tumors, has been studied in various contexts. One study with 360 patients who had gastroenteropancreatic neuroendocrine tumors (GEP-NETs) found the treatment generally safe. Most patients tolerated it well, though some experienced side effects like nausea, vomiting, and tiredness.

After Lutathera's approval and broader use, similar side effects were reported. Serious side effects, such as low blood cell counts, were less common but did occur.

The FDA has already approved Lutathera for adults with similar tumors, suggesting its safety. However, this trial focuses on understanding its effects in teenagers. While past studies support its safety, this trial will help ensure it is safe for younger patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neuroendocrine tumors?

Researchers are excited about Lutathera for neuroendocrine tumors because it represents a novel approach to treatment. Unlike traditional chemotherapy or surgery, Lutathera uses a targeted form of radiation therapy by harnessing the power of radioactive Lutetium-177. This treatment specifically targets and binds to tumor cells, delivering radiation directly to the cancer while sparing healthy tissue. This precision not only enhances the effectiveness of the treatment but also reduces side effects, offering patients a potentially more tolerable and effective option compared to existing therapies.

What evidence suggests that Lutathera might be an effective treatment for neuroendocrine tumors?

Research has shown that Lutathera, or lutetium Lu 177 dotatate, effectively treats certain neuroendocrine tumors. Studies have found that it slows the growth of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and can even stop or reduce their size. Patients receiving Lutathera often experience longer periods without disease progression compared to those treated with options like everolimus. Lutathera's approval for treating certain neuroendocrine tumors supports its effectiveness. This treatment specifically targets tumors with somatostatin receptors, a common feature in these cancers. In this trial, all eligible participants will receive Lutathera, administered with a concomitant amino acid solution, to further evaluate its efficacy in treating GEP-NETs and PPGL. ^{4 6 7 8 9}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adolescents aged 12 to <18 with advanced or metastatic GEP-NETs or PPGLs that can't be surgically removed. They must have somatostatin receptor-positive tumors, a Karnofsky score >=50 or Lansky Play-Performance Scale score >=50, and parental consent. Excluded are pregnant/breastfeeding teens, those with certain medical conditions, uncontrolled diseases, inadequate lab values, not using contraception (if applicable), known drug allergies, and other malignancies.

Inclusion Criteria

My tests show my tumor has somatostatin receptors, similar to or more than my liver.

I am between 12 and 17 years old.

My parent or guardian and I understand and agree to participate in the study.

Exclusion Criteria

Breastfeeding female patients unless they accept to discontinue breastfeeding from the 1st dose until 3 months after the last administration of study drug.

Laboratory parameters: Estimated creatinine clearance calculated by the Cockroft-Gault method < 70 mL/min; Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L; platelets <75x109/L; Total bilirubin >3 x ULN for age; Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.

You cannot have participated in any other experimental treatments in the past 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 2 weeks

Treatment

Participants receive 4 Lutathera treatments administered at 8-week intervals, with dosimetry and PK assessments during the first week after the 1st dose

32 weeks

4 visits (in-person) for Lutathera administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a short-term follow-up of 6 months and a long-term follow-up of 54 months

60 months

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium [177Lu] oxodotreotide/dotatate

Trial Overview

The trial is testing the safety and dosimetry of Lutathera in young patients with specific neuroendocrine tumors. It's an open-label study where all participants receive the same treatment without a comparison group. At least eight will be enrolled for GEP-NETs and as many as possible for PPGLs to assess how well they tolerate the drug and how it distributes in their bodies.

How Is the Trial Designed?

Group I: GEP-NET and PPGL Experimental Treatment 1 Intervention

All eligible participants will receive Lutathera (7.4 GBq/200 mCi x 4 administrations every 8 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.

Who Is Running the Clinical Trial?

Advanced Accelerator Applications

Lead Sponsor

Trials

37

Recruited

3,000+

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]

Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is a safe and effective treatment for patients with inoperable or metastatic neuroendocrine neoplasia (NEN), showing a clinical response of regressive disease in 47.6% of cases.

The study found no severe renal or hematological toxicity in 30 patients treated with Lu-DOTATATE, suggesting that while hematological parameters may influence survival, the treatment itself is well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival. Löser, A., Schwarzenböck, SM., Heuschkel, M., et al.[2018]

Peptide receptor radionuclide therapy (PRRT) using [177Lu]Lu-DOTATATE has been shown to be effective and safe for treating neuroendocrine neoplasms (NENs) across various tumor locations, with a median progression-free survival of up to 31.3 months for midgut tumors.

In a study of 522 patients, the treatment resulted in a partial response in 33.2% of cases and stable disease in 52.1%, indicating significant clinical benefit with minimal severe toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study. Mitjavila, M., Jimenez-Fonseca, P., Belló, P., et al.[2023]

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]

In a study of 219 Lutathera injections over 70 months, using a peristaltic pump (method 2) resulted in a 34.9% reduction in residual radioactivity compared to a volumetric infusion pump (method 1), indicating improved efficiency in drug delivery.

Despite method 2 having a higher cost per injection, it was reported to be safer and more suitable by operators, with no major incidents occurring during its use, suggesting it may be a better option for future radioligand therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-Dotatate administration using an infusion pump or a peristaltic pump: comparison of two methods. Donzé, C., Rubira, L., Santoro, L., et al.[2022]

Lutathera, approved in Japan in 2021, is the first peptide receptor radionuclide therapy specifically designed for treating somatostatin receptor-positive neuroendocrine tumors, providing a much-needed treatment option for these patients.

Current imaging methods in Japan for assessing somatostatin receptor expression in tumors primarily rely on In-111 pentetreotide scintigraphy, but advancements like 68Ga-DOTA-SSA PET/CT are being explored to improve evaluation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[68Ga-DOTATOC PET/CT for Diagnosing Neuroendocrine Tumors]. Koyasu, S., Shimizu, Y., Nakamoto, Y.[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 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]

Peptide receptor radionuclide therapy with (177)Lu-DOTATATE is effective for patients with metastasized or inoperable neuroendocrine tumors that show increased uptake on octreotide scintigraphy, leading to improved quality of life and partial tumor reduction or stabilization.

Side effects from this treatment are generally mild and reversible, with severe long-term side effects being rare; however, about 20% of patients may not experience any treatment effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radionuclide therapy for neuroendocrine tumours]. Mortensen, J., Oturai, P., Højgaard, L., et al.[2019]

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]

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 229 patients with advanced midgut neuroendocrine tumors, treatment with lutetium-177 (177Lu)-Dotatate significantly improved progression-free survival (65.2% at 20 months) compared to octreotide LAR alone (10.8%).

The 177Lu-Dotatate group also showed a higher response rate (18% vs. 3%) and preliminary evidence of improved overall survival, with manageable side effects, including low rates of severe myelosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. Strosberg, J., El-Haddad, G., Wolin, E., et al.[2022]

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

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