Transarterial Chemoembolization With Doxorubicin With or Without Everolimus in Treating Patients With Liver Cancer
- Conditions
- Liver Cancer
- Interventions
- Registration Number
- NCT01009801
- Lead Sponsor
- Swiss Group for Clinical Cancer Research
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoembolization kills tumor cells by carrying drugs directly into the tumor and blocking the blood flow to the tumor. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether transarterial chemoembolization with doxorubicin is more effective when given alone or when given together with everolimus in treating patients with liver cancer.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of everolimus when given together with transarterial chemoembolization with doxorubicin and to see how well it works compared with giving transarterial chemoembolization with doxorubicin alone in treating patients with liver cancer.
- Detailed Description
OBJECTIVES:
* Determine the recommended dose of everolimus in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization with doxorubicin-eluting beads (TACE). (Phase I)
* Determine the efficacy and tolerability of everolimus in patients with HCC treated with TACE as compared to TACE alone. (Phase II)
OUTLINE: This is a multicenter, dose-escalation phase I study followed by a randomized phase II study.
* Phase I: Patients receive oral everolimus once daily in the absence of disease progression or unacceptable toxicity. Beginning 7 days after the start of everolimus patients undergo transarterial chemoembolization (TACE) comprising doxorubicin-eluting beads into the hepatic artery followed in 4 weeks by an MRI. If viable tumor is found patients undergo another TACE treatment continuing every 4 weeks for up to 5 treatments.
* Phase II: Patients are stratified according to center, age (≤ 60 vs \> 60 years), and number of lesions (≤ 3 vs \> 3). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive oral placebo once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the maximum tolerated dose (MTD).
* Arm II: Patients receive oral everolimus once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.
In both arms, patients receive treatment for up to 12 months in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for analysis of AFP tumor markers. Patients also complete quality of life questionnaires, Health Economic Assessment, and EQ5D questionnaires at baseline and periodically during the study.
After completion of study treatment, patients are followed on day 30, and then every 3 months.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 27
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I doxorubicin-eluting beads Patients receive oral placebo once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD. Arm II doxorubicin-eluting beads Patients receive oral everolimus once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD. Arm I placebo Patients receive oral placebo once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD. Arm II everolimus Patients receive oral everolimus once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.
- Primary Outcome Measures
Name Time Method Dose-limiting toxicity (Phase I) after 6 weeks from registration Dose limiting toxicity (DLT) (observed within the first TACE period)
Time to progression (Phase II) 12 weeks after randomisation
- Secondary Outcome Measures
Name Time Method Tumor response according to adapted RECIST criteria (Phase II) during treatment Progression-free survival at 12 months (Phase II) within 12 months after randomisation Time to progression (Phase I) 12 weeks after registration Progression-free survival (Phase II) Time from randomization until event occurs (see description): * Relapse or progression assessed according to the modified RECIST criteria
* Death of any cause
* Metastasis outside of liverOverall survival (Phase II) Time from randomisation until death from any cause Response duration (Phase II) See description From the time when criteria for response (CR or PR) are met, until documentation of relapse or progression thereafter.
Time to treatment failure (Phase II) See description Time from registration to any treatment failure including disease progression or premature (within 12 months) discontinuation of treatment for any reason (e.g., disease progression, toxicity, patient preference, initiation of new treatment without documented progression, Initiation of second line of TACE, Initiation of sorafenib therapy or death).
Trial Locations
- Locations (8)
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Kantonsspital - St. Gallen
🇨🇭St. Gallen, Switzerland
Hopital Cantonal Universitaire de Geneve
🇨🇭Geneva, Switzerland
UniversitaetsSpital Zuerich
🇨🇭Zurich, Switzerland
Inselspital Bern
🇨🇭Bern, Switzerland
Kantonsspital Graubuenden
🇨🇭Chur, Switzerland
Clinica Luganese di Moncucco
🇨🇭Lugano, Switzerland
Institut Central des Hopitaux Valaisans / Hôpital de Sion
🇨🇭Sion, Switzerland