ABT-888 and Temozolomide for Liver Cancer

• Sponsor: Georgetown University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01205828
• Collaborator: Abbott (Industry)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 50
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Temozolomide; Drug: ABT-888	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Overall Survival [2 years]

   the number of months between a patient's enrollment and his/her date of death

2. Progression Free Survival [2 years]

   The number of months between a patient's enrollment and his/her disease progression

3. 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

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ruth He, Assistant Professor of Medicine, Georgetown University
• ClinicalTrials.gov Identifier: NCT01205828
• Other Study ID Numbers: 2009-268
• First Posted: Sep 21, 2010
• Last Update Posted: Apr 11, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Ruth He, Assistant Professor of Medicine, Georgetown University: liver cancer; hepatocellular; temozolomide; veliparib
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Temozolomide; Veliparib

Study Results

Participant Flow

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	ABT-888 40 mg daily day 1-7/28 and temozolomide 150 mg/m2/day day 1-5/28
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Temozolomide + ABT-888
Arm/Group Description	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).
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 81.3%
>=65 years	3 18.8%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	3 18.8%
Male	13 81.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 18.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 43.8%
White	4 25%
More than one race	0 0%
Unknown or Not Reported	2 12.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	ABT-888 40 mg daily day 1-7/28 and temozolomide 150 mg/m2/day day 1-5/28
Measure Participants	16
Number [participants]	3 18.8%

2. Secondary Outcome

Title	Overall Survival
Description	the number of months between a patient's enrollment and his/her date of death
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	ABT-888 40 mg daily day 1-7/28 and temozolomide 150 mg/m2/day day 1-5/28
Measure Participants	16
Median (95% Confidence Interval) [months]	13.1

3. Secondary Outcome

Title	Progression Free Survival
Description	The number of months between a patient's enrollment and his/her disease progression
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	ABT-888 40 mg daily day 1-7/28 and temozolomide 150 mg/m2/day day 1-5/28
Measure Participants	16
Median (95% Confidence Interval) [months]	1.9

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

grade 3 or 4 adverse events

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	ABT-888 40 mg daily day 1-7/28 and temozolomide 150 mg/m2/day day 1-5/28
Measure Participants	16
Number [participants]	5 31.3%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Since the treatment showed no significant efficacy against HCC, therefore study of biomarker that predict responsiveness of the treatment was not carried out.

Arm/Group Title	Temozolomide and ABT-888 in HCC Patients
Arm/Group 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 Temozolomide: Temozolomide 150 mg/m2/day PO Days 1-5 every 28 days ABT-888: ABT-888 40 mg BID PO Days 1-7 every 28 days
Measure Participants	0

Adverse Events

Time Frame	6 months
Arm/Group Title	Temozolomide + ABT-888
Arm/Group Description	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).
All Cause Mortality
	Temozolomide + ABT-888
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Temozolomide + ABT-888
	Affected / at Risk (%)	# Events
Total	6/16 (37.5%)
Gastrointestinal disorders
nausea, vomit	3/16 (18.8%)	4
bleeding	1/16 (6.3%)	1
General disorders
fatigue	1/16 (6.3%)	1
Renal and urinary disorders
multiorgan failure	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Temozolomide + ABT-888
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Blood and lymphatic system disorders
platelet count decrease	6/16 (37.5%)	6
low neutrophil	4/16 (25%)	4
low lymphocyte	4/16 (25%)	4
Gastrointestinal disorders
nausea, vomit	4/16 (25%)	4
diarrhea	2/16 (12.5%)	2
constipation	3/16 (18.8%)	3
General disorders
fatigue	7/16 (43.8%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.