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ABT-888 and Temozolomide for Liver Cancer

Primary Purpose

Hepatocellular Carcinoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Temozolomide
ABT-888
Sponsored by
Georgetown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring liver cancer, hepatocellular, temozolomide, veliparib

Eligibility Criteria

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

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

Sites / Locations

  • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temozolomide and ABT-888 in HCC patients

Arm Description

Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days ABT-888 40 mg BID PO Days 1-7 every 28 days

Outcomes

Primary Outcome Measures

Clinical Benefit Rate
complete response at any time + partial response at any time + stable disease after 8 weeks of treatment based on RECIST Criteria

Secondary Outcome Measures

Overall Survival
the number of months between a patient's enrollment and his/her date of death
Progression Free Survival
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
Record of all toxicities graded according to the NCI CTCAE version 3.0
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.

Full Information

First Posted
September 18, 2010
Last Updated
March 11, 2017
Sponsor
Georgetown University
Collaborators
Abbott
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1. Study Identification

Unique Protocol Identification Number
NCT01205828
Brief Title
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

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Terminated
Why Stopped
Lack of efficacy
Study Start Date
August 2010 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Georgetown University
Collaborators
Abbott

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
liver cancer, hepatocellular, temozolomide, veliparib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temozolomide and ABT-888 in HCC patients
Arm Type
Experimental
Arm Description
Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days ABT-888 40 mg BID PO Days 1-7 every 28 days
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
Temodar
Intervention Description
Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days
Intervention Type
Drug
Intervention Name(s)
ABT-888
Other Intervention Name(s)
Veliparib
Intervention Description
ABT-888 40 mg BID PO Days 1-7 every 28 days
Primary Outcome Measure Information:
Title
Clinical Benefit Rate
Description
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
Secondary Outcome Measure Information:
Title
Overall Survival
Description
the number of months between a patient's enrollment and his/her date of death
Time Frame
2 years
Title
Progression Free Survival
Description
The number of months between a patient's enrollment and his/her disease progression
Time Frame
2 years
Title
Number of Participants Who Had Grade 3 or 4 Adverse Events
Description
Record of all toxicities graded according to the NCI CTCAE version 3.0
Time Frame
6 months
Title
Biomarker Analysis
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aiwu R He, MD PhD
Organizational Affiliation
Georgetown University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26449224
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.
Results Reference
derived

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ABT-888 and Temozolomide for Liver Cancer

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