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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

bevacizumab

chemotherapy

embolization therapy

hepatic artery infusion

About this trial

This is an interventional treatment trial for Liver Cancer focused on measuring localized unresectable adult primary liver cancer, adult primary hepatocellular carcinoma, advanced adult primary liver cancer, recurrent adult primary liver cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed* hepatocellular carcinoma Unresectable disease Child's class A or B with liver-predominant and asymptomatic extrahepatic disease NOTE: *A highly suspicious liver mass on CT scan or MRI in the presence of alpha fetoprotein > 200 mg/dL may be used as alternative diagnostic criterion PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Absolute neutrophil count > 1,500/mm³ Platelet count > 50,000/mm³ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5.0 times upper limit of normal (ULN) Bilirubin ≤ 5.0 mg/dL Creatinine normal OR creatinine clearance > 50 mL/min No significant traumatic injury within the past 28 days No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months No serious, nonhealing wound, ulcer, or bone fracture PRIOR CONCURRENT THERAPY: No major surgery or open biopsy within the past 28 days No minor surgery (e.g., fine-needle aspirations or core biopsies) within the past 7 days No chemotherapy within the past 4 weeks No radiotherapy within the past 21 days No concurrent major surgery No other concurrent chemotherapy No other concurrent investigational drugs

Sites / Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

single arm, received bevacizumab and TACE

Arm Description

Outcomes

Primary Outcome Measures

Median Progression-free Survival

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 (TTP) of Targeted Lesions

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

Secondary Outcome Measures

TTP of Nontargeted Lesions Within the Liver

TTP of nontargeted lesions assessed via Kaplan-Meier methodology.

Overall TTP

Overall TTP assessed via Kaplan-Meier methodology.

TTP Rate at 6 Months and 1 Year

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

Overall Survival (OS)

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

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

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.

Response Rate - Based on Tumor Enhancement

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 Treatment Toxicity - Cycle 1 Pre-TACE

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 Treatment Toxicity - Cycle 1 Post-TACE

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 Treatment Toxicity - Cycles 2 and 3

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

Full Information

NCT ID

NCT00335829

First Posted

June 8, 2006

Last Updated

August 11, 2021

Sponsor

Yale University

Collaborators

National Cancer Institute (NCI), Northwestern University

1. Study Identification

Unique Protocol Identification Number

NCT00335829

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

May 2006 (undefined)

Primary Completion Date

February 2011 (Actual)

Study Completion Date

February 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

Collaborators

National Cancer Institute (NCI), Northwestern University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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. 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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Cancer

Keywords

localized unresectable adult primary liver cancer, adult primary hepatocellular carcinoma, advanced adult primary liver cancer, recurrent adult primary liver cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

single arm, received bevacizumab and TACE

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

bevacizumab

Intervention Type

Drug

Intervention Name(s)

chemotherapy

Intervention Type

Drug

Intervention Name(s)

embolization therapy

Intervention Type

Procedure

Intervention Name(s)

hepatic artery infusion

Primary Outcome Measure Information:

Title

Median Progression-free Survival

Description

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 Frame

Time through study completion, an average of 1 year

Title

Time to Tumor Progression (TTP) of Targeted Lesions

Description

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

Time Frame

6 months and 1 year

Secondary Outcome Measure Information:

Title

TTP of Nontargeted Lesions Within the Liver

Description

TTP of nontargeted lesions assessed via Kaplan-Meier methodology.

Time Frame

1 year

Title

Overall TTP

Description

Overall TTP assessed via Kaplan-Meier methodology.

Time Frame

1 year

Title

TTP Rate at 6 Months and 1 Year

Description

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

Time Frame

6 months and 1 year

Title

Overall Survival (OS)

Description

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

Time Frame

1 year

Title

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

Description

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.

Time Frame

6 months

Title

Response Rate - Based on Tumor Enhancement

Description

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.

Time Frame

6 months

Title

Safety and Treatment Toxicity - Cycle 1 Pre-TACE

Description

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.

Time Frame

Cycle 1 pre-TACE - 2 weeks

Title

Safety and Treatment Toxicity - Cycle 1 Post-TACE

Description

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

Time Frame

Cycle 1 post-TACE - 5 weeks

Title

Safety and Treatment Toxicity - Cycles 2 and 3

Description

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

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically confirmed* hepatocellular carcinoma Unresectable disease Child's class A or B with liver-predominant and asymptomatic extrahepatic disease NOTE: *A highly suspicious liver mass on CT scan or MRI in the presence of alpha fetoprotein > 200 mg/dL may be used as alternative diagnostic criterion PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Absolute neutrophil count > 1,500/mm³ Platelet count > 50,000/mm³ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5.0 times upper limit of normal (ULN) Bilirubin ≤ 5.0 mg/dL Creatinine normal OR creatinine clearance > 50 mL/min No significant traumatic injury within the past 28 days No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months No serious, nonhealing wound, ulcer, or bone fracture PRIOR CONCURRENT THERAPY: No major surgery or open biopsy within the past 28 days No minor surgery (e.g., fine-needle aspirations or core biopsies) within the past 7 days No chemotherapy within the past 4 weeks No radiotherapy within the past 21 days No concurrent major surgery No other concurrent chemotherapy No other concurrent investigational drugs

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey F. Geschwind, MD

Organizational Affiliation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Official's Role

Study Chair

Facility Information:

Facility Name

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231-2410

Country

United States

Liver Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial