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

NCT03590119 | Completed Phase 2 DMC

• 1 other identifier: NL60725.041.17
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Neuroendocrine Tumors; Liver Metastases

Keywords

LUTIA; neuroendocrine tumor; lutetium-177-dotatate; intra-arterial; liver metastases

Outcome Measures

Primary Outcomes (1)

• The 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.

  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. For each liver lobe up to three tumors (i.e. all \>3 cm) will be selected based on size (i.e. the largest lesions without central necrosis). The weighted average activity per voxel of these lesions will be divided by the normal liver tissue mean activity per voxel (i.e. a VOI with 3 cm diameter will be placed in the normal liver tissue) to calculate the T/N ratio. The T/N activity ratios of the second, third, and final treatment cycle will be assessed as secondary endpoint. Intra- and inter-patient differences will be studied.

  24 hours

Secondary Outcomes (7)

• The difference in absolute values of mean tumor and healthy liver absorbed dose on post-treatment SPECT/CT between the intra-arterial treated liver lobe and the intravenous treated liver lobe

  24 hours

• The difference in post-treatment tumor response between the intra-arterial treated liver lobe and the intravenous treated liver lobe

  3 and 6 months

• The dose-response relation between tumor absorbed dose and post-treatment tumor response

  3 and 6 months

• Toxicity and how toxicity is compared to historical controls

  6 months

• Sufficient uptake of 177Lu-dotatate in extrahepatic lesions

  24 hours

Study Arms (2)

Intra-arterially treated liver lobe

EXPERIMENTAL

Depending on the allocation after randomization, Lu-177-dotatate will be infused in either the left or the right hepatic artery, following catheterization using the Seldinger-technique.

Drug: Lutetium Lu 177-DOTATATE

'Intravenously' treated liver lobe

ACTIVE COMPARATOR

The lobe that is not treated intra-arterially, will act as the intravenously treated lobe, due to the first-pass effect.

Drug: Lutetium Lu 177-DOTATATE

Interventions

Lutetium Lu 177-DOTATATE DRUG

Intra-arterial infusion of Lu-177-DOTATATE

Also known as: Lutathera

'Intravenously' treated liver lobe; Intra-arterially treated liver lobe

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have given written informed consent.
• Female or male aged 18 years and over.
• Inoperable histologically proven neuro-endocrine tumor with indication for 177Lu-dotatate at enrollment time.
• Well-differentiated neuro-endocrine tumor with a Ki67-index ≤20% and a mitotic count of ≤20.
• Confirmed presence of somatostatin receptors on target lesions, based on somatostatin receptor imaging.
• Life expectancy of 6 months or longer.
• Eastern Cooperative Oncology Group (ECOG) performance score 0-1.
• Hepatic metastases with at least one lesion ≥3 cm on cross sectional imaging in both the right and left liver lobe (i.e. left and right lobes are based on the hepatic arterial perfusion territory).
• Presence of excessive liver metastases, defined as \>25% tumor load, with or without extrahepatic metastases.
• Patients must have clinical or radiological progressive disease.
• Negative pregnancy test for women of childbearing potential.

You may not qualify if:

• Any previous radioembolization, chemoembolization, or bland embolization, at any time, or surgery or radiofrequency ablation (or other ablative therapies) within 12 weeks prior to randomization in the study.
• Prior external beam radiation therapy to the liver.
• Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks prior to randomization in the study.
• Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 hours before and 24 hours after the administration of 177Lu-dotatate, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 4 weeks before the administration of 177Lu-dotatate, unless the tumor uptake on target lesions observed by imaging during continued Octreotide LAR treatment is higher than normal liver uptake.
• Any unresolved toxicity greater than National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE version 4.03) grade 2 from previous anti-cancer therapy.
• Serum bilirubin \> Upper Limit of Normal (ULN), serum albumin \<3.0 g/dL.
• Glomerular filtration rate \<50 ml/min.
• Hb \<5.5 mmol/L; leucocytes \<3.0x109/L; platelets \<100x109/L (at baseline; 75x109/L is sufficient for cycles 2-4).
• Uncontrolled congestive heart failure (NYHA II, III, IV).
• Uncontrolled diabetes mellitus.
• Patients suffering from diseases with an increased chance of liver toxicity.
• Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or depression. Patients who are declared incompetent.
• Previous enrolment in the present study or previous treatment with 177Lu-dotatate.
• Female patients who are not using an acceptable method of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal ligation) OR are less than 1 year postmenopausal or surgically sterile during their participation in this study (from the time they sign the consent form) to prevent pregnancy.
• Male patients who are not surgically sterile or do not use an acceptable method of contraception during their participation in this study (from the time they sign the consent form) to prevent pregnancy in a partner.

Sponsors & Collaborators

• Marnix Lam: lead

Study Sites (3)

Antoni van Leeuwenhoek Cancer Institute

Amsterdam, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

Related Publications (1)

• Ebbers SC, Braat AJAT, Moelker A, Stokkel MPM, Lam MGEH, Barentsz MW. Intra-arterial versus standard intravenous administration of lutetium-177-DOTA-octreotate in patients with NET liver metastases: study protocol for a multicenter, randomized controlled trial (LUTIA trial). Trials. 2020 Feb 5;21(1):141. doi: 10.1186/s13063-019-3888-0.

  PMID: 32024533 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Marnix GEH Lam, MD PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. dr. M.G.E.H. Lam

Model Details: This study uses a with-in subject randomization between intra-arterial treatment via the left or right hepatic artery.

Study Record Dates

• First Submitted: July 3, 2018
• First Posted: July 18, 2018
• Study Start: August 1, 2018
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: November 8, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)