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Hepatocellular CarcinomaPhase 2SORAMICNCT01126645

Sorafenib and Micro-therapy Guided by Primovist Enhanced MRI in Patients With Inoperable Liver Cancer

A Phase 2 study testing RFA and Radioembolization (SIRT) in people with Hepatocellular Carcinoma, run by University of Magdeburg at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate Sorafenib and local microtherapy guided by Primovist enhanced MRI in patients with inoperable liver cancer (HCC). Methodology: Patients with a diagnosis of hepatocellular carcinoma will receive either: local ablation therapy of liver lesions by radiofrequency ablation followed… Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
RFA and Radioembolization (SIRT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
529 participants
Where
1 siteGermany
Study dates
Dec 2010to 31 Dec 2018
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 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age: 18-85 years
  • Diagnosis of hepatocellular carcinoma
  • If primary diagnosis of HCC: diagnosis based on the following criteria:
  • cyto-histological criteria, OR
  • radiological criteria: Focal lesion >1 cm with arterial hypervascularization in 2 coincident imaging techniques (CT, MRI, or US), OR
  • combined criteria: one imaging technique showing a focal lesion 1-2 cm with arterial hypervascularization AND AFP levels >400 ng/mL, OR
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  • combined criteria: one imaging technique showing a focal lesion >2 cm with arterial hypervascularization AND AFP levels >200 ng/mL
  • If extrahepatic metastases: liver-dominant disease
  • Stage BCLC A, B, or C
  • Child-Pugh A, Child-Pugh B up to 7 points (in patients receiving anticoagulant therapy: Child-Pugh score up to 5 points; INR category not regarded for calculation of the Child-Pugh score)
  • Willing to comply with all study procedures
  • Has voluntarily given written informed consent

Who cannot join

  • If female, pregnant or breast feeding (females of child-bearing potential must use adequate contraception and must have a negative pregnancy test performed within 7 days prior to inclusion into this study)
  • If male, not using adequate birth control measures
  • One or more of the following:
  • Hemoglobin <10g/dL,
  • WBC <2,500 cells/mm3,
  • ANC <1,500 cells/mm3,
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  • platelets <50,000/mm3,
  • ECOG performance status >2
  • Life expectancy <16 weeks or medically unstable
  • Extrahepatic metastases (except metastases to bone, lymph nodes, and adrenal glands which do not constitute an exclusion criterion), but, see Additional Criteria for the Local Ablation Group, below (Section 4.2 of the study protocol)
  • Patients with known GFR <30 mL/min/1.73m2
  • PT-INR/PTT >1.5 times the upper limit of normal (patients on anticoagulation therapy will be allowed to participate provided that no prior evidence exists of an underlying abnormality in anticoagulation)
  • Uncontrolled infections at the time of microtherapy
  • Child-Pugh score >7 points; in patients receiving anticoagulant therapy: Child-Pugh score >5 points (INR category not regarded for calculation of the Child-Pugh score)
  • Uncontrolled ascites
  • Tumor load of the whole liver >70%
  • Contraindications for study medications according to product labeling or procedures (sorafenib, Primovist®, x-ray contrast agents, SIR-Spheres®, RFA, MWA, MRI, CT) incl. any contraindication to the transarterial interventional procedure (e.g., allergy against x-ray contrast agents, uncontrolled hyperthyroidism)
  • Prior resection of the papilla of Vater (e.g., Whipple procedure) or bile duct stent across the papilla
  • Significant cardiovascular disease; e.g., myocardial infarction within 6 months of inclusion, chronic heart failure (New York Heart Association class III or IV), unstable coronary artery disease
  • Uncontrolled hypertension
  • Thrombotic or embolic events including transient ischemic attacks within the past 6 months (tumor-related portal vein thrombosis allowed in the palliative part of the trial).
  • History of GI bleeding within 30 days before inclusion into this study
  • History of esophageal varices bleeding which has not been controlled by effective therapy and/or therapy to prevent bleeding recurrence
  • Previous malignancy other than carcinoma in situ of the skin or the cervix uteri within 5 years prior to inclusion
  • History of organ transplant (including prior liver transplantation)
  • HIV, congenital immune defect, any immunosuppressive therapy for autoimmune disease (rheumatoid arthritis) or inflammatory bowel disease
  • Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial
  • Close affiliation with the investigational site; e.g. first-degree relative of the investigator
  • Participating in another therapeutic clinical trial or has completed study participation in another therapeutic clinical trial within 30 days of enrolment into this trial
  • Having been previously enrolled in this clinical trial

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • University of Magdeburg

    Magdeburg, 39120

Other trials in Germany

About this study

Official title: Evaluation of Sorafenib in Combination With Local Micro-therapy Guided by Gd-EOB-DTPA Enhanced MRI in Patients With Inoperable Hepatocellular Carcinoma

The purpose of this study is to evaluate Sorafenib and local microtherapy guided by Primovist enhanced MRI in patients with inoperable liver cancer (HCC).

Methodology:

Read more

Patients with a diagnosis of hepatocellular carcinoma will receive either:

  • local ablation therapy of liver lesions by radiofrequency ablation followed by sorafenib or placebo (local ablation group), or
  • radioembolization (SIRT) + sorafenib or sorafenib alone (palliative treatment group).

In each study group, patients will be randomized to one of the two treatment arms following a pre-defined randomization plan. Randomization will be on a 1:1 basis in the local ablation group and on the basis of 10 (sorafenib only) : 11 (SIRT + sorafenib) in the palliative treatment group.

Patients in the local ablation group will be followed at 2 months intervals for recurrence and overall survival, patients in the palliative treatment group will be followed for overall survival. Follow-up in each study group will end 24 months after inclusion of the last patient into the respective study group.

The assignment of patients to the local ablation or palliative study group will be based on the ablative potential of RFA (local ablation if ≤4 tumors, each ≤5 cm in size). Diagnostic imaging will be used to guide this decision. The assignment to the local ablation or the palliative treatment group will be made by the local investigator.

As a sub-study, all patients will undergo Primovist®-enhanced MRI in addition to contrast-enhanced CT before assignment to one treatment group. The goal of the sub-study is to assess the value of Primovist®-enhanced MRI to correctly stratify patients for a local ablation or palliative treatment strategy. Primovist®-enhanced MRI will be compared with contrast-enhanced multislice CT using a truth panel assessment as the standard of reference. In addition, Primovist-enhanced MRI and contrast-enhanced CT will be obtained during follow-up of patients in the local ablation group to assess its potential for detection of recurrence.

Being tested
RFA, Radioembolization (SIRT)
Keywords
Liver, HCC
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RFAProcedure or surgery

    Also called Sorafenib (Nexavar 200 mg film-coated tablets),marketing authorization no.:EU/1/06/342/001

    A max.of 2 percutaneous RFA sessions is permitted per patient with a max.of 2 liver lesions treated in each RFA session. Randomization to sorafenib or placebo is performed after completion of RFA. Percutaneous RFA is to be performed according to the manufacturer's instructions and following as far as possible routine procedures of the participating hospital. Typically, RFA will be performed under conscious sedation, general anesthesia is permitted. After local anesthesia of the site of puncture, the applicator is positioned in the center of the lesion using ultrasound-, CT- or MR-guidance. The success of ablation is to be controlled directly after RFA using ultrasound, contrast-enhanced CT, or MR imaging. If for any reason RFA is deemed incomplete within the immediate follow-up (up to 2 weeks after the initial ablation), RFA is to be repeated once (in this case, the total (max.) number of RFA sessions will be three).

    The study procedure guide will contain further instructions for RFA.

  • Radioembolization (SIRT)Procedure or surgery

    Also called SIR Spheres Microspheres, Sorafenib (Nexavar)

    One SIRT prescription consists of the pre-treatment assessment followed by one or 2 treatment sessions The aim of pre-treatment assessment is to ensure delivery of the microspheres to the target. Evaluation includes a determination of the arterial location and any consequent necessity for coil-embolization of the gastroduodenal artery, right gastric artery and any other accessory arteries to prevent inadvertent administration of microspheres into the gastrointestinal tract or pancreas. In addition, parasitic extrahepatic supply should be coil-embolized.

    Patients in whom the shunt fraction indicates potential exposure to the lung to an absorbed radiation dose of more than 30 Gy should be excluded from treatment with SIR-Spheres. Patients who are randomized to receive SIRT but who are not regarded as eligible for SIRT after the pre-treatment assessment will be switched to the sorafenib only group within the palliative treatment arm.

Study groups in NCT01126645
Study groupRoleWhat they receive
local ablation groupOtherLocal ablation group: Potentially curative treatment of early HCC includes surgical resection and local ablation (RFA, PEI, BT). Recurrence rates after such approaches are reported to amount to 50% at 3 years and 70% at 5 years. Tumor recurrence may be either due to de novo development of new primary tumors or due to intrahepatic (unrecognized) metastases. Prevention of recurrence after local ablation is an important strategy to improve overall survival. So far, adjuvant chemoembolization and chemotherapy have not proven to be effective in preventing recurrences. There is, however, a strong rationale to assume that sorafenib will be of value in the adjuvant treatment of HCC as sorafenib has a dual mechanism of action (inhibition of tumor proliferation and antiangiogenesis) and has proven efficacy in HCC.
Receives: Procedure: RFA
palliative treatment groupActive comparatorRadioembolization has been reported to be effective in patients with unresectable HCC with preserved liver function from a number of trials. Successful downstaging of disease rendering patients eligible for potentially curative therapies, and even histologically confirmed complete responses of unresectable HCC, have repeatedly been reported providing the rationale to evaluate SIRT+sorafenib in comparison to sorafenib alone. The impact of cirrhosis as a concomitant disease in most patients with HCC is that it limits the ability of many patients to tolerate chemotherapy and is an independent cause of death in HCC patients. Thus, the historical difficulty in demonstrating an effect of therapy on survival in patients with advanced-stage, unresectable HCC (the majority). A new therapy that is effective in controlling hepatic disease, is less toxic than traditional chemotherapy, and improves the quality of life for patients in the advanced stages of HCC could represent an alternative.
Receives: Procedure: Radioembolization (SIRT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. time to recurrence

    In patients in whom local ablation therapy is appropriate, to determine if the sorafenib in combination with radiofrequency ablation (RFA) prolongs the time-to-recurrence (TTR) in comparison with RFA + placebo.

    Measured: 13-18 months (average time to recurrence)

  2. overall survival

    In patients in whom RFA is NOT appropriate (palliative treatment group), to determine if the combination of yttrium-90 microspheres (SIRT) + sorafenib improves the overall survival (OS) in comparison to sorafenib alone.

    Interim analysis will be conducted after 60 and 180 deaths and a final analysis after 240 deaths.

    Measured: 10-15 months (average survival)

  3. Primovist®-enhanced MRI is non-inferior or superior compared with contrast-enhanced multislice CT

    To confirm in a 2-step procedure that Primovist®-enhanced MRI is non-inferior (first step) or superior (second step) compared with contrast-enhanced multislice CT for assignment of patients to a palliative vs. local ablation treatment strategy.

    The overall study is successful, if the primary objectives 1 OR 2 are met, AND Primovist-enhanced MRI is at least non-inferior to contrast-enhanced CT for treatment stratification.

    Measured: 3 years

Secondary outcomes (3)

  1. quality of life

    assess health-related quality of life via ECOG questionnaire

    Measured: 3 years

  2. safety of RFA

    To assess the safety of the combination of RFA + sorafenib in comparison to RFA + placebo

    Measured: 3 years

  3. safety of SIR Spheres

    To assess the safety of the combination of SIR-Spheres therapy and sorafenib in comparison to sorafenib alone.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2010 (estimated)
  2. Study startDec 2010
  3. Primary completion25 Jan 2018
  4. Study completion31 Dec 2018

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
529 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01126645
Sponsor's protocol ID
EudraCT No. 2009-012576-27
Acronym
SORAMIC
Status last verified
May 2019
First submitted
17 May 2010
Last updated
31 May 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Schutte K, Kupcinskas J, Morkunas E, Ocal O, Schinner R, Seidensticker M, De Toni EN, Ben Khaled N, Pech M, Palmer D, Berg T, Sengel C, Basu B, Valle JW, Benckert J, Gasbarrini A, Sangro B, Malfertheiner P, Ricke J. Dynamics in Circulating Proinflammatory Biomarkers for Prognostic Assessment of Patients With Advanced HCC - A Substudy From the SORAMIC Trial. Front Gastroenterol (Lausanne). 2022 Jul 5;1:939192. doi: 10.3389/fgstr.2022.939192. eCollection 2022.

    PubMed 41822100

  • Seidensticker M, Ocal O, Schutte K, Malfertheiner P, Berg T, Loewe C, Klumpen HJ, van Delden O, Umutlu MR, Ben Khaled N, de Toni EN, Seidensticker R, Aghdassi A, Tran A, Bronowicki JP, Peynircioglu B, Sangro B, Pech M, Ricke J. Impact of adjuvant sorafenib treatment after local ablation for HCC in the phase II SORAMIC trial. JHEP Rep. 2023 Feb 15;5(5):100699. doi: 10.1016/j.jhepr.2023.100699. eCollection 2023 May.

    PubMed 36968218

  • Ricke J, Schinner R, Seidensticker M, Gasbarrini A, van Delden OM, Amthauer H, Peynircioglu B, Bargellini I, Iezzi R, De Toni EN, Malfertheiner P, Pech M, Sangro B. Liver function after combined selective internal radiation therapy or sorafenib monotherapy in advanced hepatocellular carcinoma. J Hepatol. 2021 Dec;75(6):1387-1396. doi: 10.1016/j.jhep.2021.07.037. Epub 2021 Aug 27.

    PubMed 34454995

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RFA and Radioembolization (SIRT) in people with Hepatocellular Carcinoma, run by University of Magdeburg at 1 site in Germany.

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 12 inclusion and 30 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 31 May 2019. 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 Germany. 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?

time to recurrence (time frame: 13-18 months (average time to recurrence)). The study lists 3 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 NCT01126645, which also lists 3 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 31 May 2019.

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