Neuroendocrine TumorsPhase 2ArTisaNNCT04362436
TheraSphere Selective Internal Radiation Therapy (SIRT) as Treatment for Neuroendocrine Tumours With Liver Mets
A Phase 2 study testing TheraSpheres Selective Internal Radiation Therapy (SIRT) in people with Neuroendocrine Tumors and Liver Metastases, run by Imperial College London at 1 site in United Kingdom.
Trial summary
This is an open label study for patients with inoperable metastatic neuroendocrine liver deposits to see whether treatment with Selective Internal Radiation Therapy (TheraSpheres) could lead to improved treatment response rates with acceptable toxicity (minimal serious adverse events reported). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumors, Liver Metastases
- What is being tested?
- TheraSpheres Selective Internal Radiation Therapy (SIRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Feb 2019to 15 Aug 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients must be discussed at a specialist hepatobiliary multi-disciplinary team meeting (MDT) and meet the following criteria:
- Histologically confirmed neuroendocrine tumour, with documented grade.
- >18 years of age
- Patients may be on SSAs concurrently.Patients must have had at least one previous line of therapy
- Unresectable liver only or liver predominant metastases (typically involving >25% but <60% of the liver, and technically inoperable, or unfeasible secondary to medical comorbidity)
- Have measurable disease by RECIST 1.1 criteria
Show all 16Show fewer
- Life expectancy of >12 weeks
- Eastern Cooperative Oncology Group (ECOG) / World Health Organisation (WHO) Performance Status of 0-1
- Adequate liver function (bilirubin less than 34 umol/L in the absence of a reversible cause)
- Blood work: patients must have
- Platelet count of > or = to 50x10^9/L
- Hb of > or = to 8.5g/dL
- Alanine Aminotransferase (ALT) and Aspartate transaminase (AST) < 5 x Upper limit of normal (ULN)
- Serum creatinine < 1.5 x ULN
- Internal Normalised Ration (INR) < 2.0
- Patients with portal vein thrombosis may be considered, as determined at MDT (A compromised main portal vein as demonstrated on triple-phase CT scan unless selective or super-selective SIRT can be performed and the other safety criteria are fulfilled)
Who cannot join
- Patients who meet any of the following exclusion criteria will NOT be considered eligible for this study.
- Clinically apparent ascites or other signs of hepatic failure on physical examination
- Severe uncontrollable coagulopathy
- No safe vascular access to the liver, as determined by triple phase CT
- Potential for excess radiation exposure (>30Gy) to the lungs, as determined by pretreatment 99mTc-MAA lung shunt (>20% shunt)
- Shunting to the GI tract that cannot be corrected by embolization, as demonstrated by hepatic angiogram
Show all 21Show fewer
- Previous Transarterial chemoembolization (TACE) or SIRT
- Multiple biliary stents, or ongoing cholangitis, or any intervention for, or compromise of, the Ampulla of Vater
- Previous external bean radiotherapy to the liver
- Systemic anti-cancer therapy within the last 4 weeks (excluding 1st line therapy with SSA)
- Treatment with Vascular endothelial growth factor (VEGF) inhibitors within 3 months prior to therapy
- Previous or concurrent cancer, other than Basal Cell Carcinoma, unless treated curatively 5 or more years prior to entry
- Tumour involvement of >60% of the liver
- Oesophageal bleeding during the last 3 months
- Any history of hepatic encephalopathy
- Transjugular intrahepatic portosystemic shunt (TIPS)
- Must not be at risk of hepatic or renal failure
- Contraindications against angiography
- Pregnancy and breast feeding. Women of child-bearing potential must have a negative pregnancy test 14 days before treatment, and at the time of theresphere administration.
- Subjects with another significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study.
- Must not be participating in concurrent clinical trials evaluating treatment intervention(s).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Assessment of the Safety and Efficacy of TheraSphere® Selective Internal Radiation Therapy (SIRT) in the Treatment of Metastatic (Liver) Neuroendocrine Tumours (NETs)
This is an open label study for patients with inoperable metastatic neuroendocrine liver deposits to see whether treatment with Selective Internal Radiation Therapy (TheraSpheres) could lead to improved treatment response rates with acceptable toxicity (minimal serious adverse events reported). This research will also look at the progression free survival and quality of life of the patients who decide to join the study.
Read the detailed description
Neuroendocrine tumours (NETs) are tumours which arise from cells of the neuroendocrine system, which is the mechanism by which the hypothalamus maintains homeostasis. Neuroendocrine cells secrete hormones, a type of signalling molecule, that play a role in many of the body's different processes including growth and development.
Surgical resection remains the only curative approach to NETs. However, due to non-specific representations, over 50% of NETs are unresectable at diagnosis. Patients with metastatic high grade, poorly differentiated tumours have a median overall survival of 5 months, as compared to 33 months for those with metastatic low or intermediate grade, well differentiated disease. The liver is the most common site for metastasis and is directly correlated to a much poorer prognosis if moderately to poorly differentiated disease is seen, with 5-year survival of 50% less than those without liver metastases.
Current treatment for non-resectable NETs include somatostatin analogues, systematic anti-cancer therapy (with etoposide/carboplatin being the most commonly prescribed regime), radionuclide therapy, Meta-iodobenzylguanidine Therapy (MiBGG) and Peptide Related Radiation Therapy (PRRT). The last showing great promise in clinical trials with progression free survival at 20 months of 65.2% in the Netter1 trial. However, this therapy is reliant on tumoural expression and a key density of the somatostatin 2 receptor (SSTR2), a feature that is often lost with increasing grade and aggressiveness of disease. In short, the current proposed treatments for non-resectable NETs are still to be optimised and depend heavily on patient status, SSTR2 expression and in the case of chemotherapy, is based on evidence of treatment regimens for other types of cancer.
Selective Internal Radiation Therapy (SIRT), by hepatic arterial delivery of yttrium-90 (Y-90) labelled microspheres, is a safe and effective locoregional therapy that combines a dual anticancer therapy, combining the effects of hepatic arterial embolization with targeted delivery of high dose radiation. This selectively delivers a tumouricidal dose of beta-radiation to the liver tumour, while maintaining a low radiation dose to surrounding normal tissue. 20% of the blood supply of healthy liver comes from the hepatic artery, while 90% of liver tumours derive >90% of their blood supply from the same artery and so the hepatic artery is therefore a compelling target to deliver largely tumour specific treatment, sparing healthy liver. SIRT microspheres are also small enough to get trapped in the liver microvasculature but too large to pass through capillary beds and should therefore not reach other places of the body to cause unwanted side effects.
TheraSpheres consist of an yttrium-90 containing glass microsphere. Yttrium-90 is a pure beta emitter with a half-life of approximately 64.1 hours. It has the same toxicity profile as many chemotherapy agents with the common side effects reported as fatigue, anorexia, pain, nausea and vomiting. In a past clinical trial on NETs, SIRT has shown a radiological response rate of 63% and a median survival of 70 months.
- Conditions
- Neuroendocrine Tumors, Liver Metastases
- Being tested
- TheraSpheres Selective Internal Radiation Therapy (SIRT)
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TheraSpheres Selective Internal Radiation Therapy (SIRT)Radiation
Single-photon emission computed tomography (SPECT) imaging will assess 99mTc-MAA (MAA being macro aggregated albumin) deposition in the tumour bed to estimate the dose of radiation to tumour and healthy tissue, before administration of TheraSpheres to eligible patients
| Study group | Role | What they receive |
|---|---|---|
| TheraSpheres Selective Internal Radiation Therapy (SIRT) | Experimental | Radiation therapy Receives: Radiation: TheraSpheres Selective Internal Radiation Therapy (SIRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Record incidence of adverse events overall and by severity, as well as serious adverse events using the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) for Adverse Events, version 4.03 (CTCAE V4.03)
Measured: Throughout study completion, up to 1 year
Define objective response rate (ORR)
This is the best overall response (CR+PR) determined by RECIST 1.1
Measured: Throughout study completion, up to 1 year
Secondary outcomes (4)
Progression free survival
Determined by RECIST 1.1 and defined as date of treatment to the date of first documentation of disease progression
Measured: Throughout study completion, up to 1 year
Overall survival
Date of randomisation to the date of death from any cause, or censored at date of last contact
Measured: Throughout study completion, up to 1 year
Quality of life
Evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30 (Quality of Life Questionnaire type C30) at baseline, week 8 and 3 monthly thereafter
Measured: Throughout study completion, up to 1 year
Quality of life 2
- Evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-I.NET21 (Quality of Life Questionnaire, type I.Neuroendocrine Tumour number 21) at baseline, week 8 and 3 monthly thereafter
Measured: Throughout study completion, up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2020
- Study start5 Feb 2019
- Primary completion15 Aug 2023
- Study completion15 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuroendocrine TumorsStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Biocompatibles UK Ltd
- Responsible party
- Sponsor
- Investigators
- Rohini Sharma, MD, Principal investigator, Senior Lecturer Medical Oncology and Clinical Pharmacology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04362436
- Sponsor's protocol ID
- 231087
- Acronym
- ArTisaN
- Status last verified
- Jan 2026
- First submitted
- 17 Apr 2020
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Sharma R, Slater S, Evans J, Martinez M, Ward C, Izadi H, Wernig F, Thomas R. ArTisaN trial protocol: a single Centre, open-label, phase II trial of the safety and efficacy of TheraSphere selective internal radiation therapy (SIRT) in the treatment of inoperable metastatic (liver) neuroendocrine neoplasia (NENs). BMC Cancer. 2022 Jul 20;22(1):800. doi: 10.1186/s12885-022-09859-9.
PubMed 35858849
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Assessment of the Safety and Efficacy of TheraSphere® Selective Internal Radiation Therapy (SIRT) in the Treatment of Metastatic (Liver) Neuroendocrine Tumours (NETs)
- ClinicalTrials.gov ID
- NCT04362436
- Acronym / sponsor ID
- ArTisaN / 231087
- Conditions
- Neuroendocrine Tumors, Liver Metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Biocompatibles UK Ltd
- Study start
- 5 Feb 2019 (actual)
- Primary completion
- 15 Aug 2023 (actual)
- Study completion
- 15 Aug 2023 (actual)
- First posted
- 27 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label study for patients with inoperable metastatic neuroendocrine liver deposits to see whether treatment with Selective Internal Radiation Therapy (TheraSpheres) could lead to improved treatment response rates with acceptable toxicity (minimal serious adverse events reported). This research will also look at the progression free survival and quality of life of the patients who decide to join the study.
Detailed description
Neuroendocrine tumours (NETs) are tumours which arise from cells of the neuroendocrine system, which is the mechanism by which the hypothalamus maintains homeostasis. Neuroendocrine cells secrete hormones, a type of signalling molecule, that play a role in many of the body's different processes including growth and development.
Surgical resection remains the only curative approach to NETs. However, due to non-specific representations, over 50% of NETs are unresectable at diagnosis. Patients with metastatic high grade, poorly differentiated tumours have a median overall survival of 5 months, as compared to 33 months for those with metastatic low or intermediate grade, well differentiated disease. The liver is the most common site for metastasis and is directly correlated to a much poorer prognosis if moderately to poorly differentiated disease is seen, with 5-year survival of 50% less than those without liver metastases.
Current treatment for non-resectable NETs include somatostatin analogues, systematic anti-cancer therapy (with etoposide/carboplatin being the most commonly prescribed regime), radionuclide therapy, Meta-iodobenzylguanidine Therapy (MiBGG) and Peptide Related Radiation Therapy (PRRT). The last showing great promise in clinical trials with progression free survival at 20 months of 65.2% in the Netter1 trial. However, this therapy is reliant on tumoural expression and a key density of the somatostatin 2 receptor (SSTR2), a feature that is often lost with increasing grade and aggressiveness of disease. In short, the current proposed treatments for non-resectable NETs are still to be optimised and depend heavily on patient status, SSTR2 expression and in the case of chemotherapy, is based on evidence of treatment regimens for other types of cancer.
Selective Internal Radiation Therapy (SIRT), by hepatic arterial delivery of yttrium-90 (Y-90) labelled microspheres, is a safe and effective locoregional therapy that combines a dual anticancer therapy, combining the effects of hepatic arterial embolization with targeted delivery of high dose radiation. This selectively delivers a tumouricidal dose of beta-radiation to the liver tumour, while maintaining a low radiation dose to surrounding normal tissue. 20% of the blood supply of healthy liver comes from the hepatic artery, while 90% of liver tumours derive >90% of their blood supply from the same artery and so the hepatic artery is therefore a compelling target to deliver largely tumour specific treatment, sparing healthy liver. SIRT microspheres are also small enough to get trapped in the liver microvasculature but too large to pass through capillary beds and should therefore not reach other places of the body to cause unwanted side effects.
TheraSpheres consist of an yttrium-90 containing glass microsphere. Yttrium-90 is a pure beta emitter with a half-life of approximately 64.1 hours. It has the same toxicity profile as many chemotherapy agents with the common side effects reported as fatigue, anorexia, pain, nausea and vomiting. In a past clinical trial on NETs, SIRT has shown a radiological response rate of 63% and a median survival of 70 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TheraSpheres Selective Internal Radiation Therapy (SIRT) | Experimental | Radiation: TheraSpheres Selective Internal Radiation Therapy (SIRT)Radiation therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- All patients must be discussed at a specialist hepatobiliary multi-disciplinary team meeting (MDT) and meet the following criteria:
- Histologically confirmed neuroendocrine tumour, with documented grade.
- >18 years of age
- Patients may be on SSAs concurrently.Patients must have had at least one previous line of therapy
- Unresectable liver only or liver predominant metastases (typically involving >25% but <60% of the liver, and technically inoperable, or unfeasible secondary to medical comorbidity)
Key exclusion criteria (21 listed)
- Patients who meet any of the following exclusion criteria will NOT be considered eligible for this study.
- Clinically apparent ascites or other signs of hepatic failure on physical examination
- Severe uncontrollable coagulopathy
- No safe vascular access to the liver, as determined by triple phase CT
- Potential for excess radiation exposure (>30Gy) to the lungs, as determined by pretreatment 99mTc-MAA lung shunt (>20% shunt)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TheraSpheres Selective Internal Radiation Therapy (SIRT)Single-photon emission computed tomography (SPECT) imaging will assess 99mTc-MAA (MAA being macro aggregated albumin) deposition in the tumour bed to estimate the dose of radiation to tumour and healthy tissue, before administration of TheraSpheres to eligible patients | Radiation | TheraSpheres Selective Internal Radiation Therapy (SIRT) |
Primary outcome
Incidence of adverse events
Time frame: Throughout study completion, up to 1 year
Record incidence of adverse events overall and by severity, as well as serious adverse events using the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) for Adverse Events, version 4.03 (CTCAE V4.03)
Define objective response rate (ORR)
Time frame: Throughout study completion, up to 1 year
This is the best overall response (CR+PR) determined by RECIST 1.1
4 secondary outcomes
Progression free survival
Time frame: Throughout study completion, up to 1 year
Overall survival
Time frame: Throughout study completion, up to 1 year
Quality of life
Time frame: Throughout study completion, up to 1 year
Quality of life 2
Time frame: Throughout study completion, up to 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2026.
- Derived from this study: PubMed 35858849Sharma R, Slater S, Evans J, Martinez M, Ward C, Izadi H, Wernig F, Thomas R. ArTisaN trial protocol: a single Centre, open-label, phase II trial of the safety and efficacy of TheraSphere selective internal radiation therapy (SIRT) in the treatment of inoperable metastatic (liver) neuroendocrine neoplasia (NENs). BMC Cancer. 2022 Jul 20;22(1):800. doi: 10.1186/s12885-022-09859-9.
- Individual participant dataSharing planned: Undecided
Related trials for Neuroendocrine Tumors
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 3
Somatostatin Analogues vs. Observation After Peptide Receptor Radionuclide Therapy (PRRT) in Nonfunctional Neuroendocrine Neoplasms
Neuroendocrine Neoplasm, Gastroenteropancreatic Neuroendocrine Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rohini Sharma, MD principal investigator
Senior Lecturer Medical Oncology and Clinical Pharmacology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TheraSpheres Selective Internal Radiation Therapy (SIRT) in people with Neuroendocrine Tumors and Liver Metastases, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Throughout study completion, up to 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04362436, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.