Clinical trial NCT00867321
Conditions: Liver Cancer
Keywords: adult primary hepatocellular carcinoma advanced adult primary liver cancer localized unresectable adult primary liver cancer recurrent adult primary liver cancer
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2009-04-01; Completion date: 2013-05-01
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and sorafenib may also stop the growth of liver cancer by blocking blood flow to the tumor.

PURPOSE: This randomized phase I/II trial is studying the best dose of bevacizumab when given together with sorafenib as first-line therapy in treating patients with locally advanced or metastatic liver cancer.(Phase I closed to accrual as of 11/03/2010)

Detailed description:
OBJECTIVES:

Primary

* Determine the maximum tolerated dose of bevacizumab in combination with sorafenib tosylate in patients with locally advanced or metastatic hepatocellular carcinoma. (Phase I closed to accrual as of 11/03/2010)
* Determine time to progression in these patients. (Phase II)

Secondary

* Determine the safety of this regimen in these patients. (Phase I closed to accrual as of 11/03/2010)
* Assess tolerability of this regimen in these patients. (Phase I closed to accrual as of 11/03/2010)
* Determine overall survival of these patients. (Phase II)
* Determine tumor response (at 6 months) in patients treated with this regimen. (Phase II)
* Determine progression-free survival of these patients. (Phase II)
* Determine response rate in patients treated with this regimen. (Phase II)
* Assess the occurrence of adverse events in these patients. (Phase II)

Tertiary

* Determine the relationship between tumor biomarkers and circulating biomarkers of vascular response and clinical outcome in patients treated with this regimen.

OUTLINE: This is a phase I, dose escalation study followed by a randomized phase II study.

* Phase I (closed to accrual as of 11/03/2010): Patients receive oral sorafenib tosylate twice daily on days 1-28 and bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
* Phase II: Patients are stratified according to gender (female vs male), ECOG performance status (0 vs 1), and Child-Pugh class (A vs B7). Patients are randomized to 1 of 2 treatment arms.

  * Arm I: Patients receive oral sorafenib tosylate on days 1-28 twice daily and bevacizumab IV on days 1 and 15.
  * Arm II: Patients receive oral sorafenib tosylate twice daily on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for analysis of circulating endothelial cells and circulating endothelial progenitor cells and angiogenic proteins in plasma by ELISA.

After completion of study treatment, patients are followed for 3 years.

Arms: arm 1: Patients receive oral sorafenib tosylate on days 1-28 twice daily and bevacizumab IV on days 1 and 15. arm 2: Patients receive oral sorafenib tosylate twice daily on days 1-28.
Interventions: intervention 1: bevacizumab intervention 2: sorafenib tosylate
Intervention descriptions: intervention 1: Given IV intervention 2: Given orally

Protocol documents: