A Study of ABT-888 in Combination With Temozolomide for Colorectal Cancer

• Sponsor: Georgetown University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01051596
• Collaborator: Abbott (Industry)
• Enrollment: 75
• Location: 1
• Arm: 1
• Duration (Months): 51
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

People with colorectal cancer that cannot be cured by surgery are being asked to participate in this study.

The purpose of this study is to test the efficacy (effectiveness) of a new combination of drugs, ABT-888 and temozolomide for patients with colorectal 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 colorectal cancer.

This study will help find out what effects (good and bad) the combination of drugs, temozolomide and ABT-888 has on colorectal cancer.

This research is being done because it is not known if ABT-888 will increase the effectiveness of temozolomide for colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: Temozolomide; Drug: ABT-888	Phase 2

Detailed Description

We will initiate a single arm, open label Phase II study to test the clinical activity of ABT-888 and temozolomide in patients with metastatic colorectal cancer.

Treatment will continue weekly with restaging scans to be performed every 8 weeks. The trial will follow a Simon's two-stage optimal design. For the first stage, 21 patients will be accrued. If two (9.5%) or fewer of the 21 patients exhibit a partial or complete response with ABT-888 plus temozolomide, the agent will be rejected and the trial stopped. However, if at least 3 patients of the 21 (14%) exhibit a response in the first stage, then an additional 29 patients will be entered into the second stage, for a total of 50 patients in this phase II study. If 8 (16%) or more patients exhibit a response, then the treatment will be considered for further investigation. The sample sizes of 21 and 50 patients and the decision rules, in stages 1 and 2 respectively, are designed to differentiate a 25% overall response rate from a 10% overall response rate.

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of ABT-888, an Inhibitor of Poly(ADP-ribose) Polymerase (PARP) in Combination With Temozolomide in Patients With Heavily Pretreated, Metastatic Colorectal Cancer
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABT-888 and temozolomide Temozolomide Days 1-5 and ABT-888 Days 1-7 of each 28-day cycle	Drug: Temozolomide; 150mg/m2 Days 1-5 of each 28 day cycle; Other Names: Temodar ; Drug: ABT-888; 40mg orally BID Days 1-7 of each 28 day cycle; Other Names: Veliparib

Outcome Measures

Primary Outcome Measures

1. Percent of Patients With Disease Control [2 months]

   Disease control rate defined as stable disease, partial response, or complete response according to the Response Evaluation Criteria in Solid Tumors (RECIST).

Secondary Outcome Measures

1. Median Progression-free Survival Time [1 year]

   Progression-free survival defines as the time in days from study study entry until progression or death

2. Overall Survival [1 year]

   Overall survival defined as the time in days from study entry until death

3. Percent of Patients With an Objective Response [2 months]

   Objective response rate defined as partial response or complete response according to RECIST criteria

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically proven colorectal cancer with measurable or evaluable disease

• Progression on or intolerance of or ineligibility for all standard therapies (including regimens containing fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and an anti-EGFR antibody (where appropriate))

• Age > = 18 years

• ECOG performance status 0-2

• Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intercranial disease and have not had treatment with steroids within 1 week of study enrollment

• At least 21 days since prior anti-cancer therapy, including chemotherapy, biological therapy, radiation therapy or any investigational agent within 4 weeks before starting ABT-888 and temozolomide

• Adequate hepatic, bone marrow, and renal function

• Partial thromboplastin time (PTT) must be </= 1.5 x the upper limit of institution's normal range and INR < 1.5. Subjects on anticoagulant will have PTT and INR as determined by the investigator.

• Subject's with significant fluid retention, including ascites or pleural effusion, may be allowed at the discretion of the PI

• Life expectancy > 12 weeks

• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.

• Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent approved by the IRB prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

• CNS metastases which do not meet the criteria outlined in inclusion criteria

• Active severe infection or known chronic infection with HIV, hepatitis B virus, or hepatitis C virus

• Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, myocardial infarction, stroke or congestive heart failure within the last 6 months

• Life threatening visceral disease or other severe concurrent disease

• Women who are pregnant or breastfeeding

• Anticipated patient survival under 3 months

• The subject has had another active malignancy within the past five years except for cervical cancer in site, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.

• Clinically significant and uncontrolled major medical conditions including but not limited to: active uncontrolled infection, symptomatic congestive heart failure, Unstable angina pectoris or cardiac arrhythmia, psychiatric illness/ social situation that would limit compliance with study requirements; any medical condition, which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgetown University Medical Center	Washington	District of Columbia	United States	20008

Sponsors and Collaborators

• Georgetown University
• Abbott

Investigators

• Principal Investigator: Michael J Pishvaian, MD, PhD, Georgetown University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael J Pishvaian, Assistant Professor of Medicine, Georgetown University
• ClinicalTrials.gov Identifier: NCT01051596
• Other Study ID Numbers: 2009-170
• First Posted: Jan 18, 2010
• Last Update Posted: Apr 2, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Michael J Pishvaian, Assistant Professor of Medicine, Georgetown University: metastatic; colorectal cancer
• Additional relevant MeSH terms: Colorectal Neoplasms; Temozolomide; Veliparib

Study Results

Participant Flow

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	Temozolomide Days 1-5 and ABT-888 Days 1-7 of each 28-day cycle Temozolomide: 150mg/m2 Days 1-5 of each 28 day cycle ABT-888: 40mg orally BID Days 1-7 of each 28 day cycle
Period Title: Overall Study
STARTED	75
COMPLETED	75
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	Temozolomide Days 1-5 and ABT-888 Days 1-7 of each 28-day cycle Temozolomide: 150mg/m2 Days 1-5 of each 28 day cycle ABT-888: 40mg orally BID Days 1-7 of each 28 day cycle
Overall Participants	75
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	33 44%
Male	42 56%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 4%
Not Hispanic or Latino	64 85.3%
Unknown or Not Reported	8 10.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 2.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	17 22.7%
White	48 64%
More than one race	0 0%
Unknown or Not Reported	8 10.7%

Outcome Measures

1. Primary Outcome

Title	Percent of Patients With Disease Control
Description	Disease control rate defined as stable disease, partial response, or complete response according to the Response Evaluation Criteria in Solid Tumors (RECIST).
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

Percent of patients with disease control, according to the Response Evaluation Criteria in Solid Tumors (RECIST).

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	Temozolomide Days 1-5 and ABT-888 Days 1-7 of each 28-day cycle Temozolomide: 150mg/m2 Days 1-5 of each 28 day cycle ABT-888: 40mg orally BID Days 1-7 of each 28 day cycle
Measure Participants	75
Count of Participants [Participants]	18 24%

2. Secondary Outcome

Title	Median Progression-free Survival Time
Description	Progression-free survival defines as the time in days from study study entry until progression or death
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

All patients were evaluable for response, on an intention to treat basis

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	Temozolomide Days 1-5 and ABT-888 Days 1-7 of each 28-day cycle Temozolomide: 150mg/m2 Days 1-5 of each 28 day cycle ABT-888: 40mg orally BID Days 1-7 of each 28 day cycle
Measure Participants	75
Median (95% Confidence Interval) [Months]	1.8

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival defined as the time in days from study entry until death
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

All patients were evaluable for response, on an intention to treat basis

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	Temozolomide Days 1-5 and ABT-888 Days 1-7 of each 28-day cycle Temozolomide: 150mg/m2 Days 1-5 of each 28 day cycle ABT-888: 40mg orally BID Days 1-7 of each 28 day cycle
Measure Participants	75
Median (95% Confidence Interval) [Months]	6.6

4. Secondary Outcome

Title	Percent of Patients With an Objective Response
Description	Objective response rate defined as partial response or complete response according to RECIST criteria
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

All patients were evaluable for response, on an intention to treat basis

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	Temozolomide Days 1-5 and ABT-888 Days 1-7 of each 28-day cycle Temozolomide: 150mg/m2 Days 1-5 of each 28 day cycle ABT-888: 40mg orally BID Days 1-7 of each 28 day cycle
Measure Participants	75
Count of Participants [Participants]	2 2.7%

Adverse Events

Arm/Group Title	ABT-888 and Temozolomide
Arm/Group Description	Temozolomide Days 1-5 and ABT-888 Days 1-7 of each 28-day cycle Temozolomide: 150mg/m2 Days 1-5 of each 28 day cycle ABT-888: 40mg orally BID Days 1-7 of each 28 day cycle
All Cause Mortality
	ABT-888 and Temozolomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	ABT-888 and Temozolomide
	Affected / at Risk (%)	# Events
Total	5/75 (6.7%)
Blood and lymphatic system disorders
Febrile neutropenia	1/75 (1.3%)	1
Thrombocytopenia	4/75 (5.3%)	4
Other (Not Including Serious) Adverse Events
	ABT-888 and Temozolomide
	Affected / at Risk (%)	# Events
Total	75/75 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	40/75 (53.3%)
Anemia	35/75 (46.7%)
Leucopenia	15/75 (20%)
Neutropenia	13/75 (17.3%)
Lymphopenia	2/75 (2.7%)
Urinary Hemorrhage	1/75 (1.3%)
Vaginal hemorrhage	1/75 (1.3%)
Petechiae/Purpura	1/75 (1.3%)
Edema: limb	1/75 (1.3%)
Gastrointestinal disorders
Nausea	36/75 (48%)
Vomiting	14/75 (18.7%)
Anorexia	9/75 (12%)
Diarrhea	5/75 (6.7%)
Constipation	2/75 (2.7%)
Ascites	1/75 (1.3%)
Dehydration	1/75 (1.3%)
Dysphagia	1/75 (1.3%)
Dysgeusia	1/75 (1.3%)
General disorders
Fatigue	19/75 (25.3%)
Fever	2/75 (2.7%)
Weight loss	1/75 (1.3%)
Pain NOS	3/75 (4%)
Infections and infestations
Febrile neutropenia	1/75 (1.3%)
Metabolism and nutrition disorders
Hypoalbuminemia	1/75 (1.3%)
Elevated creatinine	1/75 (1.3%)
Nervous system disorders
Neuropathy: sensory	3/75 (4%)
Dizziness	2/75 (2.7%)
Headache	1/75 (1.3%)
Respiratory, thoracic and mediastinal disorders
Shortness of breath	2/75 (2.7%)
Cough	1/75 (1.3%)
Skin and subcutaneous tissue disorders
Alopecia	1/75 (1.3%)
Peeling of feet	1/75 (1.3%)
Rash	1/75 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.