ABT-888 and Temozolomide for Liver Cancer

Study Overview
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Brief Summary
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This study is for people with liver cancer (also called hepatocellular carcinoma, or HCC in abbreviation). The purpose of this study is to test the efficacy (effectiveness) of a new combination of drugs, ABT-888 and temozolomide for patients with liver cancer. Temozolomide acts by damaging deoxyribonucleic acid (DNA) in rapidly dividing cells, in other words, cancer cells. ABT-888 inhibits an enzyme called PARP which helps to fix damaged DNA. By inhibiting this enzyme, ABT-888 prevents cancer cells from repairing the damage caused by the temozolomide and will hopefully increase the killing of cancer cells, and decrease the tumors in the body. ABT-888 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration (FDA) for use in liver cancer. This study will help find out what effects (good and bad) the combination of drugs, temozolomide and ABT-888, has on liver cancer. This research is being done because it is not known if ABT-888 will increase the effectiveness of temozolomide in liver cancer.

Detailed Description
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Patients with hepatocellular carcinoma seen at Lombardi Cancer Center were evaluated for the eligibility of this study. The Georgetown Lombardi Comprehensive Cancer Center was responsible for the data and safety monitoring of this trial. As this study is an investigator initiated study Phase II study utilizing a non-FDA approved drug for which the PI held the IND it was considered a high risk study which had real-time monitoring by the PI and study team and quarterly reviews by the LCCC Data and Safety Monitoring Committee (DSMC).

Official Title
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Phase II Study of ABT-888 and Temozolomide in Patients With Advanced Hepatocellular Carcinoma (HCC) Progressing Following Sorafenib Treatment or Intolerant to Sorafenib

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Temozolomide
* Drug: ABT-888


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological confirmation of HCC or noninvasive criteria following AASLD guidelines Measurable or evaluable disease based on RECIST criteria Progressive disease on sorafenib or intolerance to sorafenib ECOG performance status 0-2 Child Pugh Class A or B Adequate hepatic, bone marrow, and renal function Exclusion Criteria: Prior ABT-888 or other PARP inhibitor treatment Anticipation of need for major surgery during the study Any of the following within 6 months before enrollment: myocardial infarction, severe/unstable angina, congestive heart failure, or severe pulmonary disease Women who are pregnant or lactating Women and men of child-bearing potential who are not using a reliable form of contraception History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 and temozolomide Concurrent malignancy (i.e. malignancy other than hepatocellular cancer) unless 1) the subject has been curatively treated and disease free for at least 2 years or 2) the cancer was non-melanoma skin cancer or early cervical cancer. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (excluding active hepatitis B or C) or psychiatric illness/ social situations that would limit compliance with study requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide and ABT-888 in HCC patients<br>Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days ABT-888 40 mg BID PO Days 1-7 every 28 days | Drug: Temozolomide<br>* Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days<br>* Other names: Temodar;Drug: ABT-888<br>* ABT-888 40 mg BID PO Days 1-7 every 28 days<br>* Other names: Veliparib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate | complete response at any time + partial response at any time + stable disease after 8 weeks of treatment based on RECIST Criteria | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | the number of months between a patient's enrollment and his/her date of death | 2 years | 
| Progression Free Survival | The number of months between a patient's enrollment and his/her disease progression | 2 years | 
| Number of Participants Who Had Grade 3 or 4 Adverse Events | Record of all toxicities graded according to the NCI CTCAE version 3.0 | 6 months | 
| Biomarker Analysis | To evaluate biological correlation with response to ABT-888 and temozolomide, including evaluation of loss of heterozygosity (LOH) of 13q, decreased expression of or mutations in BRCA-1 or -2, and a select assortment of DNA repair genes. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver cancer, hepatocellular, temozolomide, veliparib