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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

Phase 2
18 Years
Open (Enrolling)
Colorectal Cancer

Thank you

Trial Information

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

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.

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 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

2 months

Safety Issue:


Principal Investigator

Michael J Pishvaian, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Georgetown University


United States: Food and Drug Administration

Study ID:




Start Date:

September 2009

Completion Date:

December 2013

Related Keywords:

  • Colorectal Cancer
  • metastatic
  • colorectal cancer
  • Colorectal Neoplasms



Georgetown University Medical Center Washington, District of Columbia  20007