Hepatocellular Carcinoma
Conditions
Keywords
liver cancer, hepatocellular, temozolomide, veliparib
Brief summary
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
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).
Interventions
DRUGTemozolomide
Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days
DRUGABT-888
ABT-888 40 mg BID PO Days 1-7 every 28 days
Sponsors
Abbott
Georgetown University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate | 8 weeks | complete response at any time + partial response at any time + stable disease after 8 weeks of treatment based on RECIST Criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 2 years | the number of months between a patient's enrollment and his/her date of death |
| Progression Free Survival | 2 years | The number of months between a patient's enrollment and his/her disease progression |
| Number of Participants Who Had Grade 3 or 4 Adverse Events | 6 months | Record of all toxicities graded according to the NCI CTCAE version 3.0 |
| Biomarker Analysis | 6 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Temozolomide + ABT-888 Temozolomide and ABT-888
temozolomide + ABT-888: Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days ABT-888 40 mg BID PO Days 1-7 every 28 days
Patents with stable disease or continued response to therapy will be treated and followed for a total of 6 cycles (6 months). | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Temozolomide + ABT-888 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 61 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 6 / 16 |
Outcome results
Primary
Clinical Benefit Rate
complete response at any time + partial response at any time + stable disease after 8 weeks of treatment based on RECIST Criteria
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-888 and Temozolomide | Clinical Benefit Rate | 3 participants |
Secondary
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.
Time frame: 6 months
Population: Since the treatment showed no significant efficacy against HCC, therefore study of biomarker that predict responsiveness of the treatment was not carried out.
Secondary
Number of Participants Who Had Grade 3 or 4 Adverse Events
Record of all toxicities graded according to the NCI CTCAE version 3.0
Time frame: 6 months
Population: grade 3 or 4 adverse events
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-888 and Temozolomide | Number of Participants Who Had Grade 3 or 4 Adverse Events | 5 participants |
Secondary
Overall Survival
the number of months between a patient's enrollment and his/her date of death
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABT-888 and Temozolomide | Overall Survival | 13.1 months |
Secondary
Progression Free Survival
The number of months between a patient's enrollment and his/her disease progression
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABT-888 and Temozolomide | Progression Free Survival | 1.9 months |