NCT03590119

Intra-arterial Lutetium-177-dotatate for Treatment of Patients With Neuro-endocrine Tumor Liver Metastases

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Marnix Lam · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The objective is to investigate the impact of intra-arterial administration of 177Lu-dotatate on the intrahepatic biodistribution in patients with NET liver metastases. Our primary objective is to evaluate if there is a difference in post-treatment tumor-to-non-tumor (T/N) activity concentration ratio on SPECT/CT between the intra-arterial treated liver lobe and the intravenous treated liver lobe.

Detailed description

Rationale: The majority of neuroendocrine tumor (NET) patients present with metastases, most often including liver metastases. These patients have a poorer prognosis and lower quality of life. Currently, intravenous administered somatostatin-bound radionuclides (177Lu-dotatate) have shown to improve tumor response rates and progression free survival (PFS). Despite of the increased tumor response rate and PFS, liver metastases still remain the major cause of morbidity and mortality in these patients. Patients with liver metastases have a worse outcome in terms of overall survival after treatment with 177Lu-dotatate compared to patients with limited or no liver metastases. Objective: to investigate the impact of intra-arterial (IA) administration of 177Lu-dotatate on the intrahepatic biodistribution in patients with NET liver metastases. Our primary objective is to evaluate if there is a difference in post-treatment tumor-to-non-tumor (T/N) activity concentration ratio on SPECT/CT between the intra-arterial treated liver lobe and the intravenous treated liver lobe. Study design: Multicenter, interventional, block randomized, phase 2 clinical trial. We use a within-subject controlled design where the administration of 177Lu-dotatate is randomized between the right or left hepatic artery. Selective IA administration of 177Lu-dotatate allows for intra-patient comparison between IA administration (one lobe) versus IV 'administration' (the other lobe). The contralateral liver lobe and the rest of the body receive treatment by second pass IV route. Study population: 26 patients with NET liver metastases (\> 18 years old). Intervention: Treatment will be randomized between selective right or left hepatic artery administration of 177Lu-dotatate (Four administrations of 7.4 GBq; each via the same randomly allocated hepatic artery during angiography). Main study parameters/endpoints: To assess if there is a difference in post-treatment tumor-to-non-tumor (T/N) activity concentration ratio on SPECT/CT between the intra-arterial treated liver lobe and the intravenous treated liver lobe. The T/N activity concentration will be measured on SPECT/CT. The primary endpoint will be assessed after the first treatment cycle. The T/N activity ratios of the second, third, and final treatment cycle will be assessed as secondary endpoint. Tumor response, toxicity, extrahepatic uptake and kidney uptake are secondary endpoints. Intra- and inter-patient differences will be studied. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: As with the standard IV treatment with 177Lu-dotatate, the treatment consists of four cycles. During each cycle, patients will be admitted for 1 night and undergo physical examination, laboratory examination, angiography with administration of the treatment dose, and post-treatment imaging. Risks include standard complication risks related to angiography (bleeding or infection). No additional risks with relation to the treatment itself are expected compared to the standard IV treatment (nausea, vomiting).

Conditions

• Neuroendocrine Tumors
• Liver Metastases

Interventions

Type	Name	Description
DRUG	Lutetium Lu 177-DOTATATE	Intra-arterial infusion of Lu-177-DOTATATE

Timeline

• Start date: 2018-08-01
• Primary completion: 2022-09-01
• Completion: 2022-09-01
• First posted: 2018-07-18
• Last updated: 2022-11-08

Locations

3 sites across 1 country: Netherlands