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

This study is currently recruiting participants.
Verified October 2016 by Marnix Lam, UMC Utrecht
Sponsor:
ClinicalTrials.gov Identifier:
NCT02067988
First Posted: February 20, 2014
Last Update Posted: October 27, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Marnix Lam, UMC Utrecht
  Purpose
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.

Condition Intervention Phase
Neuroendocrine Tumors Device: Holmium-166 microspheres hepatic radioembolization. Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjuvant Hepatic Holmium-166-radioembolization in Patients With Unresectable Liver Metastases of Neuroendocrine Origin, Who Have Been Treated With Lutetium-177-dotatate

Resource links provided by NLM:


Further study details as provided by Marnix Lam, UMC Utrecht:

Primary Outcome Measures:
  • Response (RECIST 1.1 Partial plus complete) [ Time Frame: 3 months ]
    To evaluate efficacy of adjuvant 166Ho-radioembolization (166Ho-RE) after systemic 177Lu-dotatate in a non-comparative phase II study


Secondary Outcome Measures:
  • Quality of Life (QoL) [ Time Frame: 3 months ]
    To evaluate QoL using EORTC questionnaire. The impact of treatment on QoL will be compared to tumour response, and other parameters. A questionnaire in the patient's native language will be provided.

  • Biodistribution [ Time Frame: 3 months ]
    To evaluate biodistribution using CT and quantitative SPECT.

  • Dosimetry [ Time Frame: 3 months ]
    To evaluate dosimetry using CT and quantitative SPECT. The imaging protocol after injection of 166Ho-PLLA-MS will consist of a dual isotope fusion SPECT/CT protocol.

  • AD Adverse events [ Time Frame: 1 year ]
    To establish the safety and toxicity profile of treatment with 166Ho-microspheres as an adjuvant treatment after 177Lu-dotatate. This profile will be established using CTCAE (incl. SAE) methodology (CTCAE version 4.03).


Estimated Enrollment: 48
Study Start Date: February 2014
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment arm
Holmium-166 microspheres hepatic radioembolization, adjuvant to systemic 177Lu-dotatate.
Device: Holmium-166 microspheres hepatic radioembolization.
Holmium-166 microspheres hepatic radioembolization.

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have given written informed consent.
  2. Female or male aged 18 years and over.
  3. Confirmed histological diagnosis NET, including bronchial carcinoids, and metastatic malignancy with liver metastases without standard therapeutic options for treatment including chemotherapy or surgery.
  4. Patients must have been treated with 4 cycles of 200 mCi 177Lu-dotatate, the last cycle within 8-12 weeks of 166Ho-RE.
  5. Life expectancy of 12 weeks or longer.
  6. World Health Organisation (WHO) Performance status 0-2.
  7. Liver disease with three or more measurable liver lesions according to the RECIST 1.1 criteria.
  8. Negative pregnancy test for women of childbearing potential.

Exclusion Criteria:

  1. 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.
  2. Radiation therapy within the last 4 weeks before the start of study therapy.
  3. The last dose of prior chemotherapy has been received less than 4 weeks prior the start of study therapy.
  4. Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy.
  5. Any unresolved toxicity greater than National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events grade 2 from previous anti-cancer therapy.
  6. Serum bilirubin > 1.5 x Upper Limit of Normal (ULN).
  7. Glomerular filtration rate <35 ml/min, determined according to the Modification of Diet in Renal Disease formula.
  8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) > 5 x ULN.
  9. Leukocytes < 3.0 x 109/l and/or platelet count < 100 x 109/l.
  10. 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.
  11. Pregnancy or nursing (women of child-bearing potential).
  12. Patients suffering from diseases with an increased chance of liver toxicity.
  13. Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or depression.
  14. Patients who are declared incompetent.
  15. Previous enrolment in the present study or previous treatment with RE.
  16. 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.
  17. 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.
  18. Patients with abnormalities of the bile ducts (such as stents) with an increased chance of infections of the bile ducts (papillotomy and cholecystectomy are allowed). Or evidence of extensive portal hypertension, splenomegaly, ascites or active hepatitis (B and/or C).
  19. Body weight over 150 kg.
  20. Severe allergy for i.v. contrast (Visipaque®), used for CT evaluation, pre-treatment angiography and treatment angiography.
  21. Liver tumour involvement ≥70% as quantified on CT.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02067988


Contacts
Contact: Marnix G Lam, MD, PhD 0031-88-7555555 m.lam@umcutrecht.nl
Contact: Tjitske Bosma, CRC 0031-88-7555555 t.bosma@umcutrecht.nl

Locations
Netherlands
University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Principal Investigator: Marnix G Lam, MD, PhD         
Sponsors and Collaborators
UMC Utrecht
Investigators
Principal Investigator: Marnix G Lam, MD, PhD UMC Utrecht, The Netherlands
  More Information

Responsible Party: Marnix Lam, MD, PhD, UMC Utrecht
ClinicalTrials.gov Identifier: NCT02067988     History of Changes
Other Study ID Numbers: NL45329.041.13
First Submitted: February 13, 2014
First Posted: February 20, 2014
Last Update Posted: October 27, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Undecided

Keywords provided by Marnix Lam, UMC Utrecht:
Radioembolization
Somatostatin receptor treatment
Neuroendocrine tumors
Liver metastases

Additional relevant MeSH terms:
Neuroendocrine Tumors
Carcinoid Tumor
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial