ABT-888 and Temozolomide for Liver Cancer

March 11, 2017 updated by: Ruth He, Georgetown University

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Temozolomide and ABT-888 in HCC patients
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
Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days
Other Names:
  • Temodar
Drug: ABT-888
ABT-888 40 mg BID PO Days 1-7 every 28 days
Other Names:
  • Veliparib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Benefit Rate
Time Frame: 8 weeks
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
Time Frame: 2 years
the number of months between a patient's enrollment and his/her date of death
2 years
Progression Free Survival
Time Frame: 2 years
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
Time Frame: 6 months
Record of all toxicities graded according to the NCI CTCAE version 3.0
6 months
Biomarker Analysis
Time Frame: 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.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Georgetown University

Collaborators

Abbott

Investigators

  • Principal Investigator: Aiwu R He, MD PhD, Georgetown University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

September 18, 2010

First Submitted That Met QC Criteria

September 18, 2010

First Posted (Estimate)

September 21, 2010

Study Record Updates

Last Update Posted (Actual)

April 11, 2017

Last Update Submitted That Met QC Criteria

March 11, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2009-268

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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