A Study of ABT-888 in Combination With Temozolomide for Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Temozolomide; ABT-888
Intervention description: 150mg/m2 Days 1-5 of each 28 day cycle; 40mg orally BID Days 1-7 of each 28 day cycle
Intervention MeSH terms: Temozolomide; Veliparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic; colorectal cancer

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.
    

Eligibility criteria:

        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