NCT01004978|CompletedPhase 3Results

Chemoembolization With or Without Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

A Phase III Randomized, Double-Blind Trial of Chemoembolization With or Without Sorafenib in Unresectable Hepatocellular Carcinoma (HCC) in Patients With and Without Vascular Invasion

National Cancer Institute (NCI)ClinicalTrials.gov

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7 other identifiers

NCI-2011-01981ECOG-E120810-00544CDR0000657952E1208U10CA021115U10CA180820

Study Type

interventional

Target

235

Locations

1 country

Sites

281

Timeline

RegisteredOct 2009

StartedOct 2009

CompletionDec 2022

Brief Summary

This randomized phase III trial studies chemoembolization and sorafenib tosylate to see how well they work compared with chemoembolization alone in treating patients with liver cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as doxorubicin hydrochloride, mitomycin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemoembolization kills tumor cells by carrying drugs directly into blood vessels near the tumor and then blocking the blood flow to allow a higher concentration of the drug to reach the tumor for a longer period of time. Kinase inhibitors, such as sorafenib tosylate may stop the growth of tumor cells by blocking the action of an abnormal protein that signals cancer cells to multiply. It is not yet known whether giving chemoembolization together with sorafenib tosylate is more effective than chemoembolization alone in treating patients with liver cancer.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

235

participants targeted

Target at P25-P50 for phase_3 hepatocellular-carcinoma

Timeline

Completed

Started Oct 2009

Longer than P75 for phase_3 hepatocellular-carcinoma

Geographic Reach

1 country

281 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

13.2 years study duration

Study Start

First participant enrolled

October 28, 2009

Completed

1 day until next milestone

First Submitted

Initial submission to the registry

October 29, 2009

Completed

1 day until next milestone

First Posted

Study publicly available on registry

October 30, 2009

Completed

11.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 11, 2021

Completed

1.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 21, 2022

Completed

2 months until next milestone

Results Posted

Study results publicly available

February 17, 2023

Completed

Last Updated

January 3, 2024

Status Verified

November 1, 2023

Enrollment Period

11.3 years

First QC Date

October 29, 2009

Results QC Date

January 19, 2023

Last Update Submit

December 6, 2023

Conditions

Hepatocellular Carcinoma Unresectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

Progression-free Survival (PFS)
PFS is defined to be the time from randomization to progression or death without evidence of progression. For cases without documentation of progression, follow-up will be censored at the date of last disease assessment without progression, unless death occurs within 4 months following the date last known progression-free, in which case the death will be counted as an event. Progression is assessed per Solid Tumor Response Criteria (RECIST) and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions.
Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years

Secondary Outcomes (3)

Overall Survival (OS)
Assessed every 3 months for 2 years and then every 6 months for 2 years
Progression-free Survival (PFS) Among Patients With Extra-hepatic Progression
Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years
Progression-free Survival (PFS) Among Patients With Intra-hepatic Progression
Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years

Other Outcomes (4)

Pharmacogenetic and Pharmacokinetic Properties of Sorafenib Including Angiogenesis, Monooxygenases, Polymorphisms and Multidrug Resistance Mutation (MDR)
Assessed at baseline, days 1, 8 and 15 of cycle 1 sorafenib, 3-5 days prior to 2nd and 3rd TACE
Inter-reader Concordance for Response by EASL (European Association for the Study of the Liver) Criteria
at 4 months and 8 months Assessed at 4 months and 8 months following initial chemoembolization
Association Between Objective Tumor Response by EASL Criteria and PFS as Well as OS
Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years
+1 more other outcomes

Study Arms (2)

Arm I (sorafenib tosylate and TACE)

EXPERIMENTAL

Patients receive sorafenib tosylate PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (closed to accrual as of 10/1/2010); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising doxorubicin-eluting beads. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI on study.

Drug: CisplatinProcedure: Computed TomographyDrug: Doxorubicin HydrochlorideDrug: Doxorubicin-Eluting BeadsOther: Laboratory Biomarker AnalysisProcedure: Magnetic Resonance ImagingDrug: MitomycinOther: Pharmacological StudyDrug: Sorafenib Tosylate

Arm II (placebo and TACE)

ACTIVE COMPARATOR

Patients receive placebo PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in Arm I. Patients also undergo CT and MRI on study.

Interventions

CisplatinDRUG

Undergo TACE

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin