ABT-888 and Temozolomide for Liver Cancer

This study has been terminated.
(Lack of efficacy)
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Ruth He, Georgetown University
ClinicalTrials.gov Identifier:
NCT01205828
First received: September 18, 2010
Last updated: March 2, 2016
Last verified: January 2016
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: Temozolomide
Drug: ABT-888
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Clinical Benefit Rate [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    the number of months between a patient's enrollment and his/her date of death

  • Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Record of all toxicities graded according to the NCI CTCAE version 3.0

  • Biomarker Analysis [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 16
Study Start Date: August 2010
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Temodar
Drug: ABT-888
ABT-888 40 mg BID PO Days 1-7 every 28 days
Other Name: Veliparib

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01205828

Locations
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
Sponsors and Collaborators
Georgetown University
Abbott
Investigators
Principal Investigator: Aiwu R He, MD PhD Georgetown University
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ruth He, Assistant Professor of Medicine, Georgetown University
ClinicalTrials.gov Identifier: NCT01205828     History of Changes
Other Study ID Numbers: 2009-268 
Study First Received: September 18, 2010
Results First Received: September 7, 2015
Last Updated: March 2, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgetown University:
liver cancer
hepatocellular
temozolomide
veliparib

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Adenocarcinoma
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Dacarbazine
Temozolomide
Veliparib
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors

ClinicalTrials.gov processed this record on May 26, 2016