Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Rare Diseases

Recurrence

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Primary Liver Cancer

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Bevacizumab

Chlorotrianisene

Liver Extracts

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

bevacizumab

chemotherapy

embolization therapy

hepatic artery infusion

Jeffrey F. Geschwind, MD

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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy 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 chemotherapy drugs directly into the tumor and blocking the blood flow to the tumor. Giving bevacizumab together with chemoembolization may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with chemoembolization works in treating patients with liver cancer that cannot be removed by surgery.

OBJECTIVES:

Primary

* Improve median progression-free survival of patients with unresectable hepatocellular cancer treated with bevacizumab and transarterial chemoembolization therapy.

Secondary

* Characterize the safety and toxicity of this regimen in these patients.
* Determine the response rate in patients treated with this regimen.

OUTLINE: Patients receive bevacizumab once in weeks 1, 3, and 5. Beginning in week 3, patients also receive transarterial chemoembolization (TACE) therapy. Treatment repeats approximately every 8 weeks for up to 3 courses. Patients achieving \< 100% necrosis by MRI after the first course receive 2 additional courses of bevacizumab and TACE.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Bevacizumab and Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery

Phase II Trial of Bevacizumab Combined With Transarterial Chemoembolization (TACE) for Hepatocellular Carcinoma

This outcome was not assessed. Instead, the primary outcome of time to tumor progression (TTP) of the targeted lesions and secondary outcomes of TTP of nontargeted lesions and overall TTP were assessed and reported.

Time to tumor progression was estimated via Kaplan-Meier methodology using the 23 patients who underwent treatment.

TTP of nontargeted lesions assessed via Kaplan-Meier methodology.

Overall TTP assessed via Kaplan-Meier methodology.

Overall TTP assessed via Kaplan-Meier methodology at 6 months and 1 year

OS assessed via Kaplan-Meier methodology both from initiation of therapy and from the date of diagnosis until death.

Efficacy as assessed by radiographic tumor response using RECIST criteria at baseline, 3 weeks after TACE, and 4 weeks after completion of final cycle.

Complete Response (CR): Disappearance of all lesions targeted by therapy Partial Response (PR): At least 30% decrease in the sum of longest diameter (LD) of lesions targeted by therapy Progressive Disease (PD): At least 20% increase in sum of LD of lesions targeted by therapy Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD.

Efficacy as assessed by radiographic tumor response utilizing the following tumor enhancement criteria:

Complete Response (CR): 100% tumor necrosis of the target lesion(s) upon completion of any of the 3 cycles of TACE therapy Partial Response (PR): Greater than 50% tumor necrosis of target lesion(s) Progressive Disease (PD): Reappearance or increased tumor enhancement greater than 25% in target lesion(s) Stable Disease (SD): Cases that do not meet CR or PR and did not demonstrate evidence of tumor progression.

Safety and toxicity assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0) for all patients (n=26) who received bevacizumab prior to TACE therapy.

Safety and toxicity assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0) for 25 who completed the first cycle of TACE and bevacizumab therapy

Safety and toxicity assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0) for patients (n=14) who completed 2 or 3 cycles of TACE and bevacizumab therapy

National Cancer Institute (NCI)

Northwestern University

Yale University

bevacizumab

chemotherapy

embolization therapy

hepatic artery infusion

Single Arm, Received Bevacizumab and TACE

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Jeff Geschwind, MD

Patients received intravenous bevacizumab (10mg/kg) and chemoembolization for up to 3 cycles over 6 months. After completion of last treatment cycle, follow-up including clinic visits and imaging was performed every 8 to 12 weeks.

PFS analysis was not conducted. No data were collected for this Outcome Measure

Median Progression-free Survival

Time to Tumor Progression (TTP) of Targeted Lesions

TTP of Nontargeted Lesions Within the Liver

Overall TTP

TTP rate at 6 months

TTP rate at 1 year

TTP Rate at 6 Months and 1 Year

OS from start of therapy

OS from date of diagnosis

Overall Survival (OS)

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Progressive Disease (PD)

Overall response rate (CR + PR)

Disease control rate (CR + PR + SD)

Response Rate - Based on Response Evaluation Criteria in Solid Tumors (RECIST)

Response Rate - Based on Tumor Enhancement

Coagulation

Fatigue

Weight loss

Ascites

Anorexia

Nausea

Vomiting

Esophageal varices

Elevated ALT

Elevated AST

Hyperbilirubinemia

Hyponatremia

Encephalopathy

Right upper quadrant pain

Proteinuria

Respiratory

Safety and Treatment Toxicity - Cycle 1 Pre-TACE

Anemia

Leukocytopenia

Lymphopenia

Edema

Ischemia

Night sweats

HEENT

Liver failure

Cellulitis

Colangitis

Hyperglycemia

Hypocalcemia

Hypokalemia

Delirium

Psychosis

Abdominal pain, not otherwise specified (NOS)

Epigastric pain

Chest pain

Pain - other

Dyspnea

Acute renal failure

1 out of the initial 26 patients did not complete the first TACE on protocol and was not included in this assessment.

Safety and Treatment Toxicity - Cycle 1 Post-TACE

Heart failure

Dermatologic

Endocrine

Duodenal perforation

Clostridium difficile

Fracture

Cord compression

Stroke

14 out of the original 26 study participants completed 2 or 3 cycles of TACE and bevacizumab therapy - adverse events associated with these patients for cycles 2 and 3 assessed.

Safety and Treatment Toxicity - Cycles 2 and 3

Overall Study

Adenocarcinoma

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Herbal and Botanical

Cola

Ronald DeMatteo, MD

RATIONALE: Embolization blocks blood flow to part of an organ and/or tumor. Blocking the portal vein on one side of the liver may cause the opposite side of the liver to increase in size and decrease the risk of liver failure following surgery.

PURPOSE: Phase II trial to study the effectiveness of portal vein embolization in treating patients who have liver metastases from primary colorectal cancer.

OBJECTIVES:

* Determine whether portal vein embolization results in significant hypertrophy of the remaining liver and potentially decreases the risk of liver failure after hepatic resection in patients with liver metastases from primary colorectal cancer.
* Determine the biologic effects of this therapy on liver metastases and normal liver parenchyma in these patients.

OUTLINE: Patients undergo portal vein embolization with 200-300 micron polyvinyl chloride particles suspended in Iohexol 300. Approximately 3-6 weeks after embolization, patients undergo an exploratory laparotomy followed by hepatic surgical resection.

Patients are followed for at least 6 months.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Portal Vein Embolization in Treating Patients With Liver Metastases From Primary Colorectal Cancer

Clinical Efficacy And Biologic Effects Of Preoperative Portal Vein Embolization In Patients With Colorectal Liver Metastases

Memorial Sloan Kettering Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bevacizumab and Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery	NCT00335829	Liver Cancer	bevacizumab chemotherapy embolization th... hepatic artery ...	18 Years - 120 Years	Yale University
Bevacizumab and Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery	NCT00335829	Liver Cancer	bevacizumab chemotherapy embolization th... hepatic artery ...	18 Years - 120 Years	Yale University
Portal Vein Embolization in Treating Patients With Liver Metastases From Primary Colorectal Cancer	NCT00028626	Colorectal Canc... Metastatic Canc...	embolization th...	18 Years -	Memorial Sloan Kettering Cancer Center
Bevacizumab and Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery	NCT00335829	Liver Cancer	bevacizumab chemotherapy embolization th... hepatic artery ...	18 Years - 120 Years	Yale University

Spots Global Cancer Trial Database for embolization therapy