Holmium-166-radioembolization in NET After Lutetium-177-dotatate; an Efficacy Study

NCT02067988 | Completed Phase 2 DMC

• 1 other identifier: NL45329.041.13
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with gastroenteropancreatic neuroendocrine tumours (NET) often die from intrahepatic disease or are excluded from liver-directed treatment because of extrahepatic disease. Adjuvant liver-directed treatment is warranted to control both intra- and extrahepatic disease. Patients with liver metastases of NET will be included in this study (n = 30-48).The efficacy and toxicity of adjuvant 166Ho-radioembolization (166Ho-RE) after systemic 177Lu-dotatate will be studied in a non-comparative phase II study. The study is an interventional, treatment, non-randomized, open label, non-comparative, phase II study. 166Ho-RE will be performed via a catheter during angiography.

Conditions

Neuroendocrine Tumors

Keywords

Radioembolization; Somatostatin receptor treatment; Neuroendocrine tumors; Liver metastases

Outcome Measures

Primary Outcomes (1)

• Response (RECIST 1.1 Partial plus complete)

  To evaluate efficacy of adjuvant 166Ho-radioembolization (166Ho-RE) after systemic 177Lu-dotatate in a non-comparative phase II study

  3 months

Secondary Outcomes (4)

• Quality of Life (QoL)

  3 months

• Biodistribution

  3 months

• Dosimetry

  3 months

• AD Adverse events

  1 year

Study Arms (1)

Treatment arm

EXPERIMENTAL

Holmium-166 microspheres hepatic radioembolization, adjuvant to systemic 177Lu-dotatate.

Device: Holmium-166 microspheres hepatic radioembolization.

Interventions

Holmium-166 microspheres hepatic radioembolization. DEVICE

Holmium-166 microspheres hepatic radioembolization.

Treatment arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), 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.
• Confirmed histological diagnosis NET, including bronchial carcinoids, and metastatic malignancy with liver metastases without standard therapeutic options for treatment including chemotherapy or surgery.
• Patients must have been treated with 4 cycles of 200 mCi 177Lu-dotatate, the last cycle within 8-12 weeks of 166Ho-RE.
• Life expectancy of 12 weeks or longer.
• World Health Organisation (WHO) Performance status 0-2.
• Liver disease with three or more measurable liver lesions according to the RECIST 1.1 criteria.
• Negative pregnancy test for women of childbearing potential.

You may not qualify if:

• Brain metastases or spinal cord compression, unless irradiated at least 4 weeks prior to the date of the experimental treatment and stable without steroid treatment for at least 1 week.
• Radiation therapy within the last 4 weeks before the start of study therapy.
• The last dose of prior chemotherapy has been received less than 4 weeks prior the start of study therapy.
• Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy.
• Any unresolved toxicity greater than National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events grade 2 from previous anti-cancer therapy.
• Serum bilirubin \> 1.5 x Upper Limit of Normal (ULN).
• Glomerular filtration rate \<35 ml/min, determined according to the Modification of Diet in Renal Disease formula.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) \> 5 x ULN.
• Leukocytes \< 3.0 x 109/l and/or platelet count \< 100 x 109/l.
• Significant cardiac event (e.g. myocardial infarction, superior vena cava (SVC) syndrome, New York Heart Association (NYHA) classification of heart disease ≥2 within 3 months before entry, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
• Pregnancy or nursing (women of child-bearing potential).
• 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 RE.

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (1)

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (6)

• Stella M, van Rooij R, Lam MGEH, de Jong HWAM, Braat AJAT. Automatic healthy liver segmentation for holmium-166 radioembolization dosimetry. EJNMMI Res. 2023 Jul 15;13(1):68. doi: 10.1186/s13550-023-00996-1.

  PMID: 37453996 DERIVED

• Stella M, Braat AJAT, Lam MGEH, de Jong HWAM, van Rooij R. 166Holmium-99mTechnetium dual-isotope imaging: scatter compensation and automatic healthy-liver segmentation for 166Holmium radioembolization dosimetry. EJNMMI Phys. 2022 Apr 21;9(1):30. doi: 10.1186/s40658-022-00459-x.

  PMID: 35445948 DERIVED

• Ebbers SC, Brabander T, Tesselaar MET, Hofland J, Braat MNGJA, Wessels FJ, Barentsz MW, Lam MGEH, Braat AJAT. Inflammatory markers and long term hematotoxicity of holmium-166-radioembolization in liver-dominant metastatic neuroendocrine tumors after initial peptide receptor radionuclide therapy. EJNMMI Res. 2022 Feb 2;12(1):7. doi: 10.1186/s13550-022-00880-4.

  PMID: 35107642 DERIVED

• Stella M, Braat A, Lam M, de Jong H, van Rooij R. Quantitative 166Ho-microspheres SPECT derived from a dual-isotope acquisition with 99mTc-colloid is clinically feasible. EJNMMI Phys. 2020 Jul 14;7(1):48. doi: 10.1186/s40658-020-00317-8.

  PMID: 32666401 DERIVED

• Braat AJAT, Bruijnen RCG, van Rooij R, Braat MNGJA, Wessels FJ, van Leeuwaarde RS, van Treijen MJC, de Herder WW, Hofland J, Tesselaar MET, de Jong HWAM, Lam MGEH. Additional holmium-166 radioembolisation after lutetium-177-dotatate in patients with neuroendocrine tumour liver metastases (HEPAR PLuS): a single-centre, single-arm, open-label, phase 2 study. Lancet Oncol. 2020 Apr;21(4):561-570. doi: 10.1016/S1470-2045(20)30027-9. Epub 2020 Feb 26.

  PMID: 32112737 DERIVED

• Braat AJAT, Kwekkeboom DJ, Kam BLR, Teunissen JJM, de Herder WW, Dreijerink KMA, van Rooij R, Krijger GC, de Jong HWAM, van den Bosch MAAJ, Lam MGEH. Additional hepatic 166Ho-radioembolization in patients with neuroendocrine tumours treated with 177Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial). BMC Gastroenterol. 2018 Jun 15;18(1):84. doi: 10.1186/s12876-018-0817-8.

  PMID: 29902988 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

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

Study Officials

• Marnix G Lam, MD, PhD

  UMC Utrecht, The Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: February 13, 2014
• First Posted: February 20, 2014
• Study Start: February 1, 2014
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: June 17, 2020

Record last verified: 2020-06

Locations

NL (1)