Outcomes of HCC (Hepatocellular Carcinoma) Patients Treated With TACE (Transarterial Chemoembolization) and Early, Not Early or Not at All Followed by Sorafenib (OPTIMIS)

OPTIMIS - Outcomes of HCC Patients Treated With TACE Followed or Not Followed by Sorafenib and the Influence of Timing to Initiate Sorafenib

This study will collect data of patients who are treated with TACE followed by sorafenib for hepatocellular carcinoma (HCC) or patients without Sorafenib after TACE. In contrast to a prior observational study on sorafenib (GIDEON study), where pre-treatment with TACE was documented retrospectively, this study will collect more detailed information about the TACE treatment and the status of a patient when treatment with sorafenib is started.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Procedure: TACE (transarterial chemoembolization); Drug: Sorafenib (Nexavar, BAY43-9006)

• Study Type: Observational
• Enrollment (Actual): 1676

Contacts and Locations

Study Locations

• Austria
  • Multiple Locations, Austria
• Brazil
  • Multiple Locations, Brazil
• Canada
  • Multiple Locations, Canada
• China
  • Multiple Locations, China
• Czechia
  • Multiple Locations, Czechia
• Denmark
  • Multiple Locations, Denmark
• Egypt
  • Multiple Locations, Egypt
• France
  • Multiple Locations, France
• Greece
  • Multiple Locations, Greece
• Hong Kong
  • Multiple Locations, Hong Kong
• Hungary
  • Multiple Locations, Hungary
• India
  • Multiple Locations, India
• Indonesia
  • Multiple Locations, Indonesia
• Israel
  • Multiple Locations, Israel
• Japan
  • Multiple Locations, Japan
• Kazakhstan
  • Multiple Locations, Kazakhstan
• Korea, Republic of
  • Multiple Locations, Korea, Republic of
• Mexico
  • Multiple Locations, Mexico
• Netherlands
  • Multiple Locations, Netherlands
• Pakistan
  • Multiple Locations, Pakistan
• Poland
  • Multiple Locations, Poland
• Russian Federation
  • Multiple Locations, Russian Federation
• Singapore
  • Multiple Locations, Singapore
• Slovakia
  • Multiple Locations, Slovakia
• Spain
  • Multiple Locations, Spain
• Sweden
  • Multiple Locations, Sweden
• Switzerland
  • Multiple Locations, Switzerland
• Taiwan
  • Multiple Locations, Taiwan
• Thailand
  • Multiple Locations, Thailand
• Turkey
  • Multiple Locations, Turkey
• Vietnam
  • Multiple Locations, Vietnam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Female and male patients with a diagnosis of hepatocellular carcinoma (HCC) will be enrolled in the participating study countries and sites during the enrollment period. All treatment decisions prior inclusion of a patient as well as during the observation must be made by the investigator based on his regular medical practice. Patients must give written informed consent prior to documentation.

During the course of the study, patients will be assigned to one of the following cohorts of special interest:

1. Patients with early start of sorafenib treatment
2. Patients without early start of sorafenib treatment.

Description

Inclusion Criteria:

• Patients with histologically/cytologically documented or radiographically diagnosed HCC. Radiographic diagnosis needs typical findings of HCC by radiographic method i.e. on multi-dimensional dynamic CT, CT hepatic arteriography (CTHA)/CT arterial portography (CTAP) or MRI.
• Patients with BCLC (Barcelona clinic liver cancer staging) stage B or higher.
• Patients in whom a decision to treat with TACE has been made at time of study enrollment. Patients that have received one TACE in the past also can be enrolled, if the TACE was done at the same site and all required data about such previous TACEs are available. TACE includes both conventional TACE with lipidiol (or similar agents) and chemotherapeutic agent(s) and TACE with DC Beads excluding TAE without chemotherapeutic agent.
• Patients with unresectable HCC (incurable with curative treatments including resection or ablation or not eligible for resection or local ablation)
• Patients must have signed an informed consent form
• Patients must have a life expectancy of at least 8 weeks

Exclusion Criteria:

• Patients who have received TACE in the past but the data about TACE required in this protocol are not available
• Patients who received any systemic anti-cancer therapy prior to the first TACE
• Patients who are treated according to a trial protocol for intervention including a locoregional therapy or systemic therapy
• Hospice patients
• All contra-indications according to the local marketing authorization should be considered.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TACE + early Nexavar; Patients with early start of Sorafenib treatment. This cohort comprises all patients where the physician decides at the time of TACE non-eligibility to choose Sorafenib as the next treatment option (regardless of whether TACE treatment is continued or not).	Procedure: TACE (transarterial chemoembolization); First treatment for all patients included in the study; Drug: Sorafenib (Nexavar, BAY43-9006)
TACE without early Nexavar; Patients without early start of Sorafenib treatment. This cohort comprises all patients where the physician decides at the time of TACE non-eligibility not to choose Sorafenib as the next treatment option. This cohort also includes patients with TACE non-eligibility for whom the decision to treat with Sorafenib is made at a later point in time, patients who are never treated with Sorafenib as well as patients for whom another systemic cancer treatment has been chosen be the physician either at time of TACE non-eligibility or at a later point in time.	Procedure: TACE (transarterial chemoembolization); First treatment for all patients included in the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Defined as time (in days) from time of TACE non-eligibility to death due to any cause. Patients lost to follow-up or alive at the end of the study will be censored at the last date known to be alive.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival from initial TACE	OS from initial TACE was defined as the time interval from the day of the first TACE to death due to any cause.	Up to 3 years
Progression-free survival (PFS) from initial TACE	PFS from initial TACE was defined as the time interval measured from the day of the first TACE to documented (radiological or clinical) progression or death, whichever came first.	Up to 3 years
Time to progression (TTP) from initial TACE	TTP from initial TACE was defined as the time interval from the day of first TACE to the date of documented progression.	Up to 3 years
Tumor response according to mRECIST criteria	Tumor response to TACE by modified Response Evaluation Criteria In Solid Tumors (mRECIST) were evaluated according to the categories "Complete Response", "Partial Response", "Stable Disease", and "Not evaluable" by mRECIST for each TACE.	Up to 3 years
Duration of TACE treatment	Duration of TACE treatment was defined as the time interval from of the day of first TACE to the date of permanent discontinuation of TACE	Up to 3 years
Number of patients with TEAEs (treatment emergent adverse events)	Patients were monitored for TEAEs using the NCI-CTCAE Version 4.03.	Up to 3 years
TACE unsuitability	TACE unsuitability was determined according to selected guidelines	Up to 3 years
Time to TACE non-eligibility	Determined according to the selected guidelines	Up to 3 years
Deterioration of liver dysfunction	Deteriorations of liver dysfunction were defined as follow: Deterioration of Child Pugh score (A5, A6, B7, B8, B9); Liver dysfunction reported as AE or deterioration of aspartate aminotransferase, alanine aminotransferase or bilirubin (from Grade 1 to Grade 2-5, from Grade 2 to 3-5, Grade 3 to Grade 4 or 5); Any liver related adverse events or deterioration of liver related events according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03; Change of liver related laboratory data (aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, prothrombin international normalized ratio [INR])	Up to 3 years
OS from initiation of sorafenib	OS from initiation of sorafenib was defined as the time interval measured from start date of sorafenib treatment to death due to any cause.	Up to 3 years
PFS from initiation of sorafenib	PFS from initiation of sorafenib was defined as the time interval measured from the start date of sorafenib treatment to documented (radiological or clinical) progression or death, whichever came first.	Up to 3 years
Tumor status at different visits response according to mRECIST	mRECIST: modified Response Evaluation Criteria In Solid Tumors	Up to 3 years
Duration of sorafenib treatment	Duration of sorafenib treatment was defined as the time interval from start date of sorafenib treatment to the date of permanent discontinuation of sorafenib treatment (regardless of the reason for discontinuation including death).	Up to 3 years
TTP from initiation of sorafenib	TTP from initiation of sorafenib was defined as the time interval from start date of sorafenib treatment to the date of documented progression.	Up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS from TACE non-eligibility	PFS from TACE non-eligibility was defined as the time interval from TACE non-eligibility to documented (radiological or clinical) progression or death, whichever came first.	Up to 3 years
TTP from TACE non-eligibility	TTP from TACE non-eligibility was defined as the time interval from TACE non-eligibility to the date of documented progression.	Up to 3 years
Tumor response from time of TACE non-eligibility by mRECIST	Planned to be evaluated according to the categories "Complete Response", "Partial Response", "Stable Disease", and "Not evaluable"	Up 3 years
Switch to sorafenib or other systemic and non-systemic cancer therapy	Evaluated according to the categories "Before initial TACE", "After one TACE", "After two TACEs", and "After more than two TACEs"	Up to 3 years
Deviations from recommendations for TACE use	Deviations from recommendations for TACE use in the treatment guidelines for TACE use based on the number of patients for whom the treatment decision for a new TACE was made by the investigator after TACE non-eligibility.	Up to 3 years
Duration of treatment of sorafenib after TACE	Defined as days from the first sorafenib dose to the date of permanent discontinuation of sorafenib plus one	Up to 3 years

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer products.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2013
• Primary Completion (Actual): July 22, 2017
• Study Completion (Actual): November 10, 2017

Study Registration Dates

• First Submitted: August 29, 2013
• First Submitted That Met QC Criteria: August 29, 2013
• First Posted (Estimate): September 2, 2013

Study Record Updates

• Last Update Posted (Actual): November 6, 2018
• Last Update Submitted That Met QC Criteria: November 5, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 16560 (Veritas IRB); NX1301 (Other Identifier: Company internal)