Trial for Microarray Analysis of Colon Cancer Outcome-A (MACCO-A)
Condition: Adenocarcinoma; Colon Cancer
MeSH terms: Adenocarcinoma; Colonic Neoplasms
Intervention: XELOX; XELIRI; Bevacizumab
Intervention description: XELOX: Oxaliplatin 130 mg/m^2 intravenously (IV); Capecitabine 825 mg/m^2 by mouth (po); XELIRI: Irinotecan 240 mg/m^2 IV; Capecitabine 825 mg/m^2 by mouth (po); 7.5 mg/kg intravenously (IV)
Intervention MeSH terms: Bevacizumab; Capecitabine; Oxaliplatin; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: colon; adenocarcinoma; adenocarcinoma-colon; adenocarcinoma-rectum

Summary:

      The purpose of this study is to determine if the investigators can predict the sensitivity or
      resistance of colon cancer to the two available first line chemotherapy agents.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provide written informed consent prior to study-specific screening procedures, with
             the understanding that the patient has the right to withdraw from the study at any
             time, without prejudice

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Patients with metastatic, Response Evaluation Criteria In Solid Tumors (RECIST)
             measurable, adenocarcinoma of the colon and/or rectum are eligible provided their
             disease is metastatic to the liver. The liver metastatic disease should be confirmed
             cytologically or histologically at the time of study biopsy or prior to the study
             biopsy. All pre-study scans documenting disease must be done < 4 weeks prior to
             registration.

          -  Patients must have had no prior treatment with either irinotecan or oxaliplatin.

          -  Prior adjuvant therapy with fluoropyrimidine is allowed.

          -  Prior radiotherapy is allowed, but patients should have measurable disease outside the
             radiation port and/or progressive disease within the previously radiated volume. In
             addition, it must be at least 2 weeks since administration of radiation therapy and
             all signs of toxicity must have abated.

          -  Patients must have adequate renal and hepatic function (creatinine < 1.6 and
             calculated creatinine clearance [Cockcroft-Gault equation] > 60 ml/min; bilirubin <
             2.0; and serum glutamic oxaloacetic transaminase [SGOT] less than 3 x normal limits)
             obtained within 4 weeks prior to registration.

          -  Alkaline phosphatase < 2.5 x upper normal limit (or < 5 x upper normal limit in the
             case of liver metastases or < 10 x upper normal limit in the case of bone disease)

          -  Patients must have absolute neutrophil count (ANC) > 1500/mm³ and platelet count >
             100,000/mm³ within 4 weeks prior to registration.

          -  Have a negative serum or urine pregnancy test within 7 days prior to starting therapy
             (female patients of childbearing potential)

        Exclusion Criteria:

          -  Pregnant and breast-feeding women are excluded from the study because effects on the
             fetus are unknown and there may be a risk of increased fetal wastage.

          -  Women of childbearing potential with either a positive or no pregnancy test (serum or
             urine) at baseline. Women/men of childbearing potential not using a reliable and
             appropriate contraceptive method. (Postmenopausal women must have been amenorrheic for
             at least 12 months to be considered of non-childbearing potential.) Patients will
             agree to continue contraception for 30 days from the date of the last study drug
             administration.

          -  Serious, uncontrolled, concurrent infection(s). Patients must have no evidence of
             significant active infection (e.g., pneumonia, peritonitis, wound abscess, etc.) at
             time of study entry.

          -  Life expectancy < 3 months

          -  Any prior fluoropyrimidine therapy (unless given in an adjuvant setting and completed
             at least 6 months earlier)

          -  Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity
             to 5-fluorouracil or known dihydropyrimidine dehydrogenase (DPD) deficiency

          -  Treatment for other carcinomas within the last 5 years, except cured non-melanoma skin
             and treated in-situ cervical cancer

          -  Participation in any investigational drug study

          -  Clinically significant cardiac disease of New York Heart Association Class III or
             greater (e.g. congestive heart failure, symptomatic coronary artery disease and
             cardiac arrhythmias not well controlled with medication) or myocardial infarction
             within the last 12 months.

          -  Evidence of central nervous system (CNS) metastases (unless CNS metastases have been
             stable for > 3 months) or history of uncontrolled seizures, central nervous system
             disorders or psychiatric disability judged by the investigator to be clinically
             significant, precluding informed consent, or interfering with compliance of oral drug
             intake.

          -  Other serious uncontrolled medical conditions that the investigator feels might
             compromise study participation

          -  Major surgery, open biopsy, or significant trauma injury within 28 days prior to Day 0

          -  Lack of physical integrity of the upper gastrointestinal tract or malabsorption
             syndrome

          -  Known, existing uncontrolled coagulopathy

          -  Impaired renal function (estimated creatinine clearance < 60ml/min as calculated with
             Cockcroft-Gault equation

          -  Unwillingness to give written informed consent

          -  Unwillingness to participate or inability to comply with the protocol for the duration
             of the study

          -  Urine protein: creatinine ratio > 1.0 at screening

          -  Blood pressure of > 150/100 mmHg

          -  Unstable angina

          -  Clinically significant peripheral vascular disease

          -  Arterial thrombotic events, stroke or transient ischemic attack (TIA) within the last
             6 months