Linifanib in Treating Patients With Advanced, Refractory Colorectal Cancer
Condition: Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer
MeSH terms: Rectal Neoplasms; Colonic Neoplasms; Recurrence
Intervention: linifanib
Intervention description: Given PO
Intervention MeSH terms: Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well Linifanib works in treating patients with advanced,
      refractory colorectal cancer expressing k-Ras mutations. Linifanib may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed colorectal cancer refractory to at least 1 but no more than 3
             systemic chemotherapy regimens

          -  Patients must have received one standard chemotherapy regimen in the metastatic
             setting

          -  Established Ras-mutant tumor status (archived specimens are okay and this test can
             have been performed at local laboratories)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

          -  The subject must have adequate bone marrow and organ function, defined as follows:

          -  Hemoglobin ≥ 9g/dL

          -  Platelets >100,000,

          -  Absolute neutrophil count (ANC) > 1000/uL,

          -  Serum creatinine < 1.5 x upper limit of normal,

          -  Total bilirubin < 1.5 x the upper limit of normal,

          -  AST and ALT ≤ 2.0 x upper limit of normal (or ≤ 5 x ULN in the presence of liver
             metastases)

          -  Measurable disease, defined as at least 1 unidimensionally measurable lesion on a
             computed tomography (CT) scan or magnetic resonance imaging (MRI) as defined by
             Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

          -  Female subjects of childbearing potential must have a negative urine or serum
             pregnancy test within 7 days of study treatment; surgically sterile and/or
             postmenopausal women must be amenorrheic for at least 12 months to be considered of
             non-child-bearing potential

          -  Female subjects of child-bearing potential and male subjects must agree to use
             adequate contraception prior to study entry, for the duration of study participation
             and up to two months after the last dose of ABT 869; adequate contraception methods
             should be used consistently and correctly and include the following:

          -  Total abstinence from sexual intercourse (minimum one complete menstrual cycle)

          -  A vasectomized partner

          -  Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior
             to study drug administration

          -  Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with
             spermicidal jellies or cream)

          -  The subject must be willing and able to comply with the protocol for the duration of
             the study, including undergoing treatment and scheduled visits and examinations

          -  The subject must have given written informed consent prior to the initiation of any
             screening or study-specific procedures

          -  Ability to understand and the willingness to sign a written informed consent; a signed
             informed consent must be obtained prior to any study-specific procedures

          -  Patients must be at least 14 days status post last day of prior chemotherapy (at least
             28 days since last dose of bevacizumab) and have recovered to grade =< 1 from all
             chemotherapy-associated side effects

          -  Patients must have the ability to swallow pills

        Exclusion Criteria:

          -  Untreated central nervous system (CNS) metastases; patients may have CNS metastases
             from any timeframe as long as they are treated and not progressing; brain imaging is
             not required if there is no clinical suspicion of brain metastases

          -  Pregnant or lactating females are excluded

          -  Uncontrolled hypertension defined as systolic blood pressure (BP) > 140 and/or
             diastolic BP > 90 initially evaluated on day of study eligibility determination (when
             laboratory parameters are assessed), but must be maintained on day of study
             initiation; (If a patient is found to have a value outside the range above, repeat BP
             may be assessed and if at subsequent readings x 2 (taken in clinic at least 15 minutes
             apart) criteria are met, the patient can then be eligible; initiation or modification
             of antihypertensives is allowed to achieve adequate BP for eligibility; finally, in
             the case that subsequent determinations are required, the BP assessment that counts
             towards eligibility is the reading on the day of study initiation); (note: a clinic BP
             reading without the patient having been at rest for 15 minutes or with the wrong cuff
             size can be repeated the same day for eligibility criteria to be determined

          -  Active bleeding or history of bleeding from cancer related events

          -  History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) or
             recent myocardial infarction (MI) (< 6 months)

          -  Active ulcerative colitis, Crohn's disease or Celiac disease that could interfere with
             the absorption of the drug

          -  Current use of therapeutic anticoagulation; low dose anticoagulation for catheter
             prophylaxis is permitted; Lovenox is permitted for prophylaxis; (Note: patients who
             develop thrombosis and are placed on anticoagulation while on this trial may continue
             on study at the discretion of the investigator)

          -  The subject has had major surgery within 28 days of Study Day 1

          -  The subject has had radiation therapy within 14 days of Study Day 1

          -  The subject had prior bevacizumab within 28 days of study day 1

          -  No prior treatment with vascular endothelial growth factor (VEGF) receptor tyrosine
             kinase inhibitors; prior treatment with other investigational agents is allowed

          -  The subject has a medical condition, which in the opinion of the study investigator,
             places them at unacceptably high risk for toxicities

          -  Other active malignancy for which the patient has been treated within the past one
             year

          -  Subjects with known human immunodeficiency virus (HIV) infection are excluded

          -  Subject has documented left ventricular ejection fraction (LVEF) < 50%

          -  Subject has Proteinuria > grade 1 at baseline measured by urine dipstick (2+ or
             greater) and confirmed by 24 hour (hr) urine collection (> = 1g/24hrs)