Bevacizumab and Sorafenib as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Liver Cancer
|ClinicalTrials.gov Identifier: NCT00867321|
Recruitment Status : Completed
First Posted : March 23, 2009
Results First Posted : July 2, 2017
Last Update Posted : July 2, 2017
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)
|Condition or disease||Intervention/treatment||Phase|
|Liver Cancer||Biological: bevacizumab Drug: sorafenib tosylate||Phase 1 Phase 2|
- 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)
- 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)
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Randomized Trial of Sorafenib and Bevacizumab as First-Line Therapy in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma|
|Study Start Date :||April 2009|
|Actual Primary Completion Date :||April 2012|
|Actual Study Completion Date :||May 2013|
Experimental: Arm I (Phase II)
Patients receive oral sorafenib tosylate on days 1-28 twice daily and bevacizumab IV on days 1 and 15.
Given IVDrug: sorafenib tosylate
Experimental: Arm II (Phase II)
Patients receive oral sorafenib tosylate twice daily on days 1-28.
Drug: sorafenib tosylate
- Maximum Tolerated Dose (Phase I) [ Time Frame: From baseline up to 3 years post treatment ]MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients). If dose level (-1) is not tolerable, but dose (-3) or (-2) is below or at MTD, testing of alternate dose levels (-2a, -3a, -3b) will occur as outlined in the table. The number of dose limiting toxicities will be reported here.
- Time to Progression (TTP) (Phase II) [ Time Frame: From baseline up to 3 years post treatment ]Time to progression is defined to be the length of time from study registration to a) date of disease progression as defined by section 11.0, or b) last follow-up. If a patient dies without documentation of disease progression, the patient will be considered to have had a tumor progression at the time of death unless there is sufficient documented evidence to conclude no progression occurred prior to death. Kaplan-Meier survival curves will be used to estimate the distribution of TTP.
- Overall Survival [ Time Frame: Up to 3 years post treatment ]Overall survival (OS) is defined as the length of time from date of registration to a) date of death due to any cause or b) last follow-up. Kaplan-Meier survival curves will be used to estimate the distribution of OS.
- Tumor Response at 6 Months [ Time Frame: 6 months ]Tumor response (at 6 months) is defined as the number of responses (complete or partial response per Section 11) over the number of eligible patients observed for at least 6 months. Tumor response will be evaluated using simple estimates of proportions.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00867321
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|Study Chair:||Steven R. Alberts, MD||Mayo Clinic|