Clinical trial NCT01205828: ABT-888 and Temozolomide for Liver Cancer
Official title: Phase II Study of ABT-888 and Temozolomide in Patients With Advanced Hepatocellular Carcinoma (HCC) Progressing Following Sorafenib Treatment or Intolerant to Sorafenib
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: liver cancer
hepatocellular
temozolomide
veliparib
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2010-09-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Clinical Benefit Rate
timeFrame: 8 weeks
Secondary outcomes:
measure: Overall Survival
timeFrame: 2 years
measure: Progression Free Survival
timeFrame: 2 years
measure: Number of Participants Who Had Grade 3 or 4 Adverse Events
timeFrame: 6 months
measure: Biomarker Analysis
timeFrame: 6 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
Study officials:
affiliation: Georgetown University
name: Aiwu R He, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gabrielson A, Tesfaye AA, Marshall JL, Pishvaian MJ, Smaglo B, Jha R, Dorsch-Vogel K, Wang H, He AR. Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 2015 Nov;76(5):1073-9. doi: 10.1007/s00280-015-2852-2. Epub 2015 Oct 8.