Hepatocellular CarcinomaPhase 2NASIR-HCCNCT03380130
A Study of the Safety and Antitumoral Efficacy of Nivolumab After SIRT for the Treatment of Patients With HCC
A Phase 2 study testing Nivolumab and SIR-Spheres in people with Hepatocellular Carcinoma, run by Clinica Universidad de Navarra, Universidad de Navarra at 9 sites in Spain.
Trial summary
The purpose of this study is to evaluate the effect of the anti-programmed death 1 (PD-1) agent nivolumab following selective internal radiation therapy (SIRT) for patients with unresectable hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Nivolumab and SIR-Spheres
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 9 sitesSpain
- Study dates
- 11 Sep 2017to 4 Nov 2020
- 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
- Diagnosis of HCC based on histology or non-invasive criteria if cirrhotics. Patients with fibrolamellar carcinoma are not excluded.
- Cirrhosis absent, non-viral or due to hepatitis C or B virus infection. Subjects with chronic hepatitis B virus infection must be on effective antiviral therapy
- Preserved liver function (without cirrhosis or with compensated cirrhosis in Child Pugh Class A).
- ECOG performance status 0 or 1
- Willing to have a liver biopsy pre-treatment
- Considered candidates for locoregional therapy using SIR-Spheres based on
Show all 21Show fewer
- the absence of extrahepatic disease (patients with regional lymph nodes < 2 cm in short axis are accepted)
- unsuitability for liver resection or transplantation, or percutaneous ablation
- considered not good candidates for TACE because they have; Single tumors larger than 5 cm. Multiple tumors that cannot be targeted superselectively. Unilobar tumors with segmental or lobar portal vein thrombosis.
- At least one measurable lesion by RECIST 1.1 criteria.
- Adequate organ and marrow function as evidenced by:
- White blood cell count ≥ 2000/μL.
- Neutrophils ≥ 1000/μL.
- Platelets ≥ 60 x 103/μL.
- Hemoglobin ≥ 9.0 g/dL.
- Creatinine Clearance > 40 mL/min.
- AST and ALT ≤ 5 X ULN
- Bilirubin ≤ 2 mg/dL
- INR ≤ 1.8.
- Albumin ≥ 3.0 g/dL
- Willing and able to comply with immune-monitoring sample collection and required study follow-up.
Who cannot join
- Any history of hepatic encephalopathy
- Any prior (within 6 months) or current clinical ascites.
- Any history of clinically meaningful variceal bleeding within the last three months.
- Active coinfection with both hepatitis B and C or hepatitis D infection in subjects with hepatitis B
- Occlusive main trunk portal vein thrombosis or absence of intrahepatic portal blood flow if patient carries a portocaval shunt.
- Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
Show all 12Show fewer
- Any autoimmune disease that may require immunosuppressive therapy.
- Any severe organ disease
- Prior therapy with any drug specifically targeting T-cell costimulation or checkpoint pathways.
- Prior organ allograft or allogeneic bone marrow transplantation
- Active bacterial or fungal infections within 7 days of study entry.
- Any condition requiring systemic treatment with corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Spain9 sites
Hospital Universitario de Cruces
Barakaldo
Hospital Clinic
Barcelona
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario Gregorio Marañon
Madrid
Hospital Universitario Ramon y Cajal
Madrid
Hospital Universitario Central de Asturias
Oviedo
Clinica Universidad de Navarra
Pamplona, 31008
Hospital Universitario Donostia
San Sebastián
Hospital Universitario Lozano Blesa
Zaragoza
About this study
Official title: A Multicenter, Open-label, Single-arm Study of the Safety and Antitumoral Efficacy of Nivolumab After SIRT Using SIR-Spheres for the Treatment of Patients With HepatoCellular Carcinoma That Are Candidates for Locoregional Therapies
The purpose of this study is to evaluate the effect of the anti-programmed death 1 (PD-1) agent nivolumab following selective internal radiation therapy (SIRT) for patients with unresectable hepatocellular carcinoma (HCC).
SIRT using yttrium90-loaded microspheres is increasingly used to treat patients with HCC, particularly those that are not good candidates for transarterial chemoembolization or TACE. SIRT induces disease control (objective tumor remission or stabilization) in most patients while progression usually results from the growth of new lesions. SIR-Spheres are resin-made microspheres used for SIRT.
Read more
On the other hand, nivolumab is under clinical development for the treatment of more advanced HCC. Available data in patients that mostly had progression to other therapies and vascular involvement or metastatic disease show significant systemic antitumor activity that results in durable objective remissions and disease stabilizations.
Therefore, in patients with HCC that has not spread beyond the liver, the systemic action of nivolumab may improve the anti-tumor effect of SIRT. Furthermore, by inducing immunogenic tumor cell death, SIRT may have a synergistic effect with nivolumab.
Read the detailed description
Worldwide, intra-arterial therapies are the mainstay of the treatment of patients with HCC in the intermediate stage or in the advanced stage because of portal vein invasion. While transarterial chemoembolization (TACE) is the most widely applied intra-arterial therapy, not all patients in the intermediate stage are good candidates for this procedure and TACE is formally contraindicated in the presence of portal vein invasion. Selective Internal Radiation Therapy (SIRT) using yttrium90-loaded microspheres is increasingly used to treat such patients that are not good candidates for TACE. SIR-Spheres are resin-made microspheres extensively used for SIRT and there is consistent level 2 evidence of its activity in HCC. SIRT induces disease control (partial objective remission or tumor stabilization) in the majority of patients while progression usually results from the growth of new lesions.
Nivolumab is under clinical development for the treatment of advanced stage HCC. Preliminary data in a population that mostly had progression to other therapies, vascular involvement or metastatic disease suggest significant systemic antitumor activity that results in durable objective remissions and disease stabilizations. In patients with HCC that has not spread beyond the liver, the systemic action of nivolumab may improve the anti-tumor effect of SIRT by providing eradication or sustained tumor growth control of residual disease in treated lesions and other locations (intrahepatic or extrahepatic micrometastasis). Furthermore, by inducing immunogenic tumor cell death, SIRT may have a synergistic effect with immune checkpoint inhibitors including nivolumab. Besides, SIRT and nivolumab are by and large well tolerated. The sequential use of SIRT and nivolumab could have strong antitumor activity and a favorable safety profile and therefore deserves to be tested in patients with intermediate to advanced tumor stages.
The primary objective of the study is therefore to evaluate the safety of nivolumab in combination with SIRT using SIR-Spheres. The secondary objective is to evaluate the anti-tumor activity of nivolumab in combination with SIRT using SIR-Spheres. Exploratory objectives are to evaluate the role of blood and tissue biomarkers in determining the anti-tumor activity of nivolumab in combination with SIRT using SIR-Spheres; to evaluate the utility of baseline or on-treatment soluble markers that may serve as surrogate markers of efficacy; and to explore the role of the ALBI score in predicting patient outcomes.
SIRT will be performed as a single-day treatment using SIR-Spheres resin microspheres as detailed in Gil-Alzugaray et al. 2013. Three weeks after SIRT, patients will start receiving nivolumab every 2 weeks until completion of 8 courses of 3 bi-weekly nivolumab doses, toxicity, or tumor progression defined using RECIST 1.1 criteria. Patients will be allowed to continue nivolumab treatment beyond progression under strict protocol-defined circumstances. All subjects will undergo tumor assessments at every q6 week for the first year, and then q12 week thereafter until radiographic progression. Patients will complete a follow-up Visit 100 days from the last dose of nivolumab and will then be followed for overall survival.
Patients with all etiologies could be recruited. Those with chronic hepatitis B will be on antiviral therapy per regional standard of care guidelines. Patients with chronic hepatitis C may receive treatment for this condition with direct antiviral agents during the treatment period as per local practice guidelines.
A tumor sample obtained before SIRT and blood samples obtained before SIRT and before and after nivolumab will be used for correlative biomarker studies.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Nivolumab, SIR-Spheres
- Keywords
- Hepatocellular Carcinoma, Liver cancer, Hepatoma
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
An anti-programmed death 1 monoclonal antibody
SIR-SpheresDevice
Also called radioembolization, transarterial radioembolization (TARE)
Resin microspheres labeled with the radioactive isotope yttrium 90 that serves as a source of beta radiation
| Study group | Role | What they receive |
|---|---|---|
| SIRT and Nivolumab | Experimental | SIRT (selective internal radiation therapy) will be performed in a single session using SIR-Spheres resin microspheres. After 3 weeks, nivolumab 240 mg every 2 weeks will be initiated Receives: Drug: Nivolumab; Device: SIR-Spheres |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate and type of adverse events, liver decompensation, and transient and permanent drug discontinuations due to toxicity.
The incidence of observed adverse events (AE) will be evaluated according to NCI CTCAE version 4.03. Particular attention will be given to adverse events that may follow enhanced T cell activation (hepatitis, dermatitis, colitis, pneumonitis, endocrinopathy or other immune-mediated AEs) and radiation damage to non-target organs (REILD, radiation pneumonitis and GI ulcers).
Measured: Two years
Secondary outcomes (7)
Response rate
Measured: Two years
Disease control rate
Measured: Two years
Duration of response
Measured: From date of complete or partial response to the date of progression, assessed up to 36 months.
Time to progression
Measured: From date of SIRT to the date of progression, assessed up to 36 months.
Progression-free survival
Measured: From date of SIRT to the date of progression or death, whichever came first, assessed up to 36 months.
Overall survival
Measured: From date of SIRT to the date of death, assessed up to 36 months
Pattern of progression according to RECIST 1.1 criteria.
Event that trigers the evaluation of tumor assessment as progressive disease according to RECIST 1.1 criteria, subclassified as 1) growth of existing tumor lesions only; 2) occurrence of new lesions inside the liver irrespective of previous criterion; and 3) occurrence of new lesions outside the liver irrespective of the two prior criteria.
Measured: Two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2017
- Study start11 Sep 2017
- Primary completion1 Mar 2020
- Study completion4 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- 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
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinica Universidad de Navarra, Universidad de Navarra
- Sponsor type
- University, hospital or other
- Collaborators
- Sirtex Medical, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Bruno Sangro, MD, Principal investigator, Liver Unit, Clínica Universidad de Navarra
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03380130
- Sponsor's protocol ID
- NASIR-HCC/CA209-992
- Acronym
- NASIR-HCC
- Status last verified
- Nov 2020
- First submitted
- 20 Oct 2017
- Last updated
- 4 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sangro B, Salem R. Transarterial chemoembolization and radioembolization. Semin Liver Dis. 2014 Nov;34(4):435-43. doi: 10.1055/s-0034-1394142. Epub 2014 Nov 4.
PubMed 25369305Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, Raoul JL, Sangro B. Heterogeneity of patients with intermediate (BCLC B) Hepatocellular Carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012 Nov;32(4):348-59. doi: 10.1055/s-0032-1329906. Epub 2013 Feb 8.
PubMed 23397536Sangro B, Carpanese L, Cianni R, Golfieri R, Gasparini D, Ezziddin S, Paprottka PM, Fiore F, Van Buskirk M, Bilbao JI, Ettorre GM, Salvatori R, Giampalma E, Geatti O, Wilhelm K, Hoffmann RT, Izzo F, Inarrairaegui M, Maini CL, Urigo C, Cappelli A, Vit A, Ahmadzadehfar H, Jakobs TF, Lastoria S; European Network on Radioembolization with Yttrium-90 Resin Microspheres (ENRY). Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011 Sep 2;54(3):868-78. doi: 10.1002/hep.24451. Epub 2011 Jun 30.
PubMed 21618574Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PubMed 19097774Gil-Alzugaray B, Chopitea A, Inarrairaegui M, Bilbao JI, Rodriguez-Fraile M, Rodriguez J, Benito A, Dominguez I, D'Avola D, Herrero JI, Quiroga J, Prieto J, Sangro B. Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology. 2013 Mar;57(3):1078-87. doi: 10.1002/hep.26191. Epub 2013 Feb 15.
PubMed 23225191El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.
PubMed 28434648De la Torre-Alaez M, Matilla A, Varela M, Inarrairaegui M, Reig M, Lledo JL, Arenas JI, Lorente S, Testillano M, Marquez L, Iserte G, Argemi J, Gomez-Martin C, Rodriguez-Fraile M, Bilbao JI, Pollock RF, Pohlmann J, Agirrezabal I, Sangro B. Health-related quality of life in patients with unresectable hepatocellular carcinoma treated with SIRT and nivolumab: a sub-analysis of the NASIR-HCC trial. J Patient Rep Outcomes. 2025 Apr 8;9(1):39. doi: 10.1186/s41687-025-00873-6.
PubMed 40198533de la Torre-Alaez M, Matilla A, Varela M, Inarrairaegui M, Reig M, Lledo JL, Arenas JI, Lorente S, Testillano M, Marquez L, Da Fonseca L, Argemi J, Gomez-Martin C, Rodriguez-Fraile M, Bilbao JI, Sangro B. Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: a phase 2, single-arm study. J Immunother Cancer. 2022 Nov;10(11):e005457. doi: 10.1136/jitc-2022-005457.
PubMed 36450386Ezponda A, Rodriguez-Fraile M, Morales M, Vivas I, De La Torre M, Sangro B, Bilbao JI. Hepatic Flow Redistribution is Feasible in Patients with Hepatic Malignancies Undergoing Same-Day Work-Up Angiography and Yttrium-90 Microsphere Radioembolization. Cardiovasc Intervent Radiol. 2020 Jul;43(7):987-995. doi: 10.1007/s00270-019-02371-x. Epub 2019 Dec 17.
PubMed 31848672
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Single-arm Study of the Safety and Antitumoral Efficacy of Nivolumab After SIRT Using SIR-Spheres for the Treatment of Patients With HepatoCellular Carcinoma That Are Candidates for Locoregional Therapies
- ClinicalTrials.gov ID
- NCT03380130
- Acronym / sponsor ID
- NASIR-HCC / NASIR-HCC/CA209-992
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma, Liver cancer, Hepatoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Clinica Universidad de Navarra, Universidad de NavarraUniversity, hospital or other
- Collaborators
- Sirtex Medical, Bristol-Myers Squibb
- Study start
- 11 Sep 2017 (actual)
- Primary completion
- 1 Mar 2020 (actual)
- Study completion
- 4 Nov 2020 (actual)
- First posted
- 20 Dec 2017 (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.
The purpose of this study is to evaluate the effect of the anti-programmed death 1 (PD-1) agent nivolumab following selective internal radiation therapy (SIRT) for patients with unresectable hepatocellular carcinoma (HCC).
SIRT using yttrium90-loaded microspheres is increasingly used to treat patients with HCC, particularly those that are not good candidates for transarterial chemoembolization or TACE. SIRT induces disease control (objective tumor remission or stabilization) in most patients while progression usually results from the growth of new lesions. SIR-Spheres are resin-made microspheres used for SIRT.
On the other hand, nivolumab is under clinical development for the treatment of more advanced HCC. Available data in patients that mostly had progression to other therapies and vascular involvement or metastatic disease show significant systemic antitumor activity that results in durable objective remissions and disease stabilizations.
Therefore, in patients with HCC that has not spread beyond the liver, the systemic action of nivolumab may improve the anti-tumor effect of SIRT. Furthermore, by inducing immunogenic tumor cell death, SIRT may have a synergistic effect with nivolumab.
Detailed description
Worldwide, intra-arterial therapies are the mainstay of the treatment of patients with HCC in the intermediate stage or in the advanced stage because of portal vein invasion. While transarterial chemoembolization (TACE) is the most widely applied intra-arterial therapy, not all patients in the intermediate stage are good candidates for this procedure and TACE is formally contraindicated in the presence of portal vein invasion. Selective Internal Radiation Therapy (SIRT) using yttrium90-loaded microspheres is increasingly used to treat such patients that are not good candidates for TACE. SIR-Spheres are resin-made microspheres extensively used for SIRT and there is consistent level 2 evidence of its activity in HCC. SIRT induces disease control (partial objective remission or tumor stabilization) in the majority of patients while progression usually results from the growth of new lesions.
Nivolumab is under clinical development for the treatment of advanced stage HCC. Preliminary data in a population that mostly had progression to other therapies, vascular involvement or metastatic disease suggest significant systemic antitumor activity that results in durable objective remissions and disease stabilizations. In patients with HCC that has not spread beyond the liver, the systemic action of nivolumab may improve the anti-tumor effect of SIRT by providing eradication or sustained tumor growth control of residual disease in treated lesions and other locations (intrahepatic or extrahepatic micrometastasis). Furthermore, by inducing immunogenic tumor cell death, SIRT may have a synergistic effect with immune checkpoint inhibitors including nivolumab. Besides, SIRT and nivolumab are by and large well tolerated. The sequential use of SIRT and nivolumab could have strong antitumor activity and a favorable safety profile and therefore deserves to be tested in patients with intermediate to advanced tumor stages.
The primary objective of the study is therefore to evaluate the safety of nivolumab in combination with SIRT using SIR-Spheres. The secondary objective is to evaluate the anti-tumor activity of nivolumab in combination with SIRT using SIR-Spheres. Exploratory objectives are to evaluate the role of blood and tissue biomarkers in determining the anti-tumor activity of nivolumab in combination with SIRT using SIR-Spheres; to evaluate the utility of baseline or on-treatment soluble markers that may serve as surrogate markers of efficacy; and to explore the role of the ALBI score in predicting patient outcomes.
SIRT will be performed as a single-day treatment using SIR-Spheres resin microspheres as detailed in Gil-Alzugaray et al. 2013. Three weeks after SIRT, patients will start receiving nivolumab every 2 weeks until completion of 8 courses of 3 bi-weekly nivolumab doses, toxicity, or tumor progression defined using RECIST 1.1 criteria. Patients will be allowed to continue nivolumab treatment beyond progression under strict protocol-defined circumstances. All subjects will undergo tumor assessments at every q6 week for the first year, and then q12 week thereafter until radiographic progression. Patients will complete a follow-up Visit 100 days from the last dose of nivolumab and will then be followed for overall survival.
Patients with all etiologies could be recruited. Those with chronic hepatitis B will be on antiviral therapy per regional standard of care guidelines. Patients with chronic hepatitis C may receive treatment for this condition with direct antiviral agents during the treatment period as per local practice guidelines.
A tumor sample obtained before SIRT and blood samples obtained before SIRT and before and after nivolumab will be used for correlative biomarker studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SIRT and Nivolumab | Experimental | Drug: Nivolumab, Device: SIR-SpheresSIRT (selective internal radiation therapy) will be performed in a single session using SIR-Spheres resin microspheres. After 3 weeks, nivolumab 240 mg every 2 weeks will be initiated |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Diagnosis of HCC based on histology or non-invasive criteria if cirrhotics. Patients with fibrolamellar carcinoma are not excluded.
- Cirrhosis absent, non-viral or due to hepatitis C or B virus infection. Subjects with chronic hepatitis B virus infection must be on effective antiviral therapy
- Preserved liver function (without cirrhosis or with compensated cirrhosis in Child Pugh Class A).
- ECOG performance status 0 or 1
- Willing to have a liver biopsy pre-treatment
Key exclusion criteria (12 listed)
- Any history of hepatic encephalopathy
- Any prior (within 6 months) or current clinical ascites.
- Any history of clinically meaningful variceal bleeding within the last three months.
- Active coinfection with both hepatitis B and C or hepatitis D infection in subjects with hepatitis B
- Occlusive main trunk portal vein thrombosis or absence of intrahepatic portal blood flow if patient carries a portocaval 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 |
|---|---|---|
| NivolumabAlso: OpdivoAn anti-programmed death 1 monoclonal antibody | Drug | SIRT and Nivolumab |
| SIR-SpheresAlso: radioembolization, transarterial radioembolization (TARE)Resin microspheres labeled with the radioactive isotope yttrium 90 that serves as a source of beta radiation | Device | SIRT and Nivolumab |
Primary outcome
Rate and type of adverse events, liver decompensation, and transient and permanent drug discontinuations due to toxicity.
Time frame: Two years
The incidence of observed adverse events (AE) will be evaluated according to NCI CTCAE version 4.03. Particular attention will be given to adverse events that may follow enhanced T cell activation (hepatitis, dermatitis, colitis, pneumonitis, endocrinopathy or other immune-mediated AEs) and radiation damage to non-target organs (REILD, radiation pneumonitis and GI ulcers).
7 secondary outcomes
Response rate
Time frame: Two years
Disease control rate
Time frame: Two years
Duration of response
Time frame: From date of complete or partial response to the date of progression, assessed up to 36 months.
Time to progression
Time frame: From date of SIRT to the date of progression, assessed up to 36 months.
Progression-free survival
Time frame: From date of SIRT to the date of progression or death, whichever came first, assessed up to 36 months.
Overall survival
Time frame: From date of SIRT to the date of death, assessed up to 36 months
Pattern of progression according to RECIST 1.1 criteria.
Time frame: Two years
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 4 Nov 2020.
- Background: PubMed 25369305Sangro B, Salem R. Transarterial chemoembolization and radioembolization. Semin Liver Dis. 2014 Nov;34(4):435-43. doi: 10.1055/s-0034-1394142. Epub 2014 Nov 4.
- Background: PubMed 23397536Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, Raoul JL, Sangro B. Heterogeneity of patients with intermediate (BCLC B) Hepatocellular Carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012 Nov;32(4):348-59. doi: 10.1055/s-0032-1329906. Epub 2013 Feb 8.
- Background: PubMed 21618574Sangro B, Carpanese L, Cianni R, Golfieri R, Gasparini D, Ezziddin S, Paprottka PM, Fiore F, Van Buskirk M, Bilbao JI, Ettorre GM, Salvatori R, Giampalma E, Geatti O, Wilhelm K, Hoffmann RT, Izzo F, Inarrairaegui M, Maini CL, Urigo C, Cappelli A, Vit A, Ahmadzadehfar H, Jakobs TF, Lastoria S; European Network on Radioembolization with Yttrium-90 Resin Microspheres (ENRY). Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011 Sep 2;54(3):868-78. doi: 10.1002/hep.24451. Epub 2011 Jun 30.
- Background: PubMed 19097774Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
- Background: PubMed 23225191Gil-Alzugaray B, Chopitea A, Inarrairaegui M, Bilbao JI, Rodriguez-Fraile M, Rodriguez J, Benito A, Dominguez I, D'Avola D, Herrero JI, Quiroga J, Prieto J, Sangro B. Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology. 2013 Mar;57(3):1078-87. doi: 10.1002/hep.26191. Epub 2013 Feb 15.
- Background: PubMed 28434648El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.
- Derived from this study: PubMed 40198533De la Torre-Alaez M, Matilla A, Varela M, Inarrairaegui M, Reig M, Lledo JL, Arenas JI, Lorente S, Testillano M, Marquez L, Iserte G, Argemi J, Gomez-Martin C, Rodriguez-Fraile M, Bilbao JI, Pollock RF, Pohlmann J, Agirrezabal I, Sangro B. Health-related quality of life in patients with unresectable hepatocellular carcinoma treated with SIRT and nivolumab: a sub-analysis of the NASIR-HCC trial. J Patient Rep Outcomes. 2025 Apr 8;9(1):39. doi: 10.1186/s41687-025-00873-6.
- Derived from this study: PubMed 36450386de la Torre-Alaez M, Matilla A, Varela M, Inarrairaegui M, Reig M, Lledo JL, Arenas JI, Lorente S, Testillano M, Marquez L, Da Fonseca L, Argemi J, Gomez-Martin C, Rodriguez-Fraile M, Bilbao JI, Sangro B. Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: a phase 2, single-arm study. J Immunother Cancer. 2022 Nov;10(11):e005457. doi: 10.1136/jitc-2022-005457.
- Derived from this study: PubMed 31848672Ezponda A, Rodriguez-Fraile M, Morales M, Vivas I, De La Torre M, Sangro B, Bilbao JI. Hepatic Flow Redistribution is Feasible in Patients with Hepatic Malignancies Undergoing Same-Day Work-Up Angiography and Yttrium-90 Microsphere Radioembolization. Cardiovasc Intervent Radiol. 2020 Jul;43(7):987-995. doi: 10.1007/s00270-019-02371-x. Epub 2019 Dec 17.
- Individual participant dataSharing planned: No
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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.
Bruno Sangro, MD principal investigator
Liver Unit, Clínica Universidad de Navarra
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and SIR-Spheres in people with Hepatocellular Carcinoma, run by Clinica Universidad de Navarra, Universidad de Navarra at 9 sites in Spain.
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 21 inclusion and 12 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 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Spain. 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?
Rate and type of adverse events, liver decompensation, and transient and permanent drug discontinuations due to toxicity. (time frame: Two years). 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 NCT03380130, which also lists 9 linked publications.
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 4 Nov 2020.