A Multi-Center, Open Label, Parallel Group, Randomised, Phase IIB Clinical Trial to Evaluate the Safety and Efficacy of CoFactor and 5-FU Versus Leucovorin and 5-FU in Subjects With Metastatic Colorectal Carcinoma
- Have surgically incurable, confirmed metastatic colon or rectal adenocarcinoma.
- Be male or non-pregnant, non-lactating female subjects ≥ 18 years of age.
- If female, and of childbearing potential, agree to use adequate contraception (as
deemed by the investigator) throughout their participation in this study and for 30
days after discontinuation of study medication.
- If, female of childbearing potential, have a negative pregnancy test prior to the
start of the study.
- Have a life expectancy of at least 6 months.
- Have radiologically or clinically measurable disease for response assessment.
Presence of ascites or pleural effusion(s) are not acceptable as single sites of
response assessment, but may be present if dimensional or other discrete measurable
disease is present for evaluation.
- Have an ECOG Performance Level of 0-2 (or Karnofsky of 100-70). A lower ECOG or
Karnofsky is acceptable only if clearly due to non-oncologic conditions (e.g., prior
paraplegia from polio).
- Have had no prior chemotherapy for established, metastatic disease. (Subjects may
have received adjuvant chemotherapy with fluoropyrimidine therapy).
- Have at least 6 months elapsed since prior adjuvant 5-FU or CPT-11 therapy, or
Mitomycin C or nitrosourea therapy.
- Have had at least an 8 week interval since any prior radiation therapy or 4 weeks
since any major surgery.
- Have recovered from any toxicities resulting from prior therapies (except for
- Adequate renal, bone marrow, liver function defined as serum creatinine less than
1.5 times the upper limit of normal, serum bilirubin less than 2 times the upper
limit of normal, ANC greater than 1.5 x 109/L, Platelet count greater than 90 x
109/L, SGOT (AST) and SGPT (ALT) less than 3 times the upper limit of normal.
- Failure by the subject or the subject's legal representative to sign the Informed
- An inability to obtain Informed Consent because of psychiatric or complex medical
- Have concurrent infection including diagnoses of FUO or evidence of possible central
line sepsis (subjects must be afebrile at the start of therapy).
- Have unstable oncologic emergency syndromes: superior vena cava (SVC) syndrome,
rising bilirubin needing stent placement, spinal cord compression, progressive brain
metastases, active bleeding, hypercalcemia, etc.
- Have unstable medical conditions such as acute coronary syndrome, cardio-vascular
accident within the previous 12 months (such as transient ischemic attacks,
accelerated hypertension), etc.
- Have cerebellar neurologic syndromes such as Parkinson's disease, multiple sclerosis,
- Have a known intolerance to fluoropyrimidine (5-FU, Capecitabine, Floxuridine, UFT)
therapy (dihydropyrimidine dehydrogenase deficiency).
- Patients with vomiting, diarrhea, or nausea of grade greater than 1.
- Received any investigational drug or agent/procedure, i.e. participation in another
trial within 4 weeks before beginning treatment with study drug.