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

March 10, 2019 updated by: Michael J Pishvaian, Georgetown University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

75

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, 20008
        • 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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression-free Survival Time
Time Frame: 1 year
Progression-free survival defines as the time in days from study study entry until progression or death
1 year
Overall Survival
Time Frame: 1 year
Overall survival defined as the time in days from study entry until death
1 year
Percent of Patients With an Objective Response
Time Frame: 2 months
Objective response rate defined as partial response or complete response according to RECIST criteria
2 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: Michael J Pishvaian, 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

September 1, 2009

Primary Completion (Actual)

June 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

January 8, 2010

First Submitted That Met QC Criteria

January 15, 2010

First Posted (Estimate)

January 18, 2010

Study Record Updates

Last Update Posted (Actual)

April 2, 2019

Last Update Submitted That Met QC Criteria

March 10, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2009-170

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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