Gemcitabine in Combination With Pemetrexed Long Term Infusion in the Treatment of Pretreated Metastatic Colorectal Cancer Patients

Inclusion Criteria:

1. Histologic or cytologic confirmed diagnosis of colorectal carcinoma with metastatic (STAGE IV) disease.
2. Measurable disease according to RECIST criteria
3. Prior chemotherapy for metastatic disease is required; prior regimens (in adjuvant oral advanced stage setting) must include 5fluorouracile, Oxaliplatin and Irinotecan if not contraindicated.
4. At least a 4-week interval between the last dose of chemotherapy and study registration.
5. Recovery from all prior treatment-related toxicities to CTC \<= grade 1 (except alopecia)
6. Male or female, aged \>= 18 years
7. Life expectancy of greater than 12 weeks.
8. ECOG performance status \<= 2
9. Patients must have normal organ and marrow function as defined below:

   * leukocytes \>=3,000/microL
   * absolute neutrophil count \>=1,500/microL
   * hemoglobin \>= 9 g/dl
   * platelets \>=100,000/microL
   * serum total bilirubin \<= 1.5 X institutional upper limit of normal
   * AST(SGOT)/ALT(SGPT) \<= 2.5 X institutional upper limit of normal (\<= 5 times the upper institutional limits of normal if hepatic metastases are present)
   * serum creatinine \<= 1.5 times the institutional upper limits of normal
   * Creatinine Clearance \> 45 ml/min
10. The effects of Gemcitabine and Pemetrexed on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because therapeutic agents used in this trial are known to be teratogenic, female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception (hormonal or barrier method of birth control; abstinence) during the study and for 3 months thereafter. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
11. Participant is willing and able to give informed consent for participation in the study. Voluntary signed and dated written informed consent form in accordance with regulatory and institutional guidelines obtained before the performance of any protocol-related procedures not part of normal patient care.

Exclusion Criteria:

1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
2. Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
3. Previous treatment with Gemcitabine or Pemetrexed.
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Gemcitabine and/or Pemetrexed or other agents used in the study
5. Patients with active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
6. Past or current history of neoplasm other than colorectal carcinoma with a disease-free interval of less than 5 years, except for non-melanoma skin cancer or curatively treated carcinoma in situ of the cervix.
7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
8. Inability to interrupt aspirin or other non-steroidal anti-inflammatory agents 2 days before, the day of, and 2 days after the dose of pemetrexed single agent or pemetrexed plus carboplatin.
9. HIV-positivity, whether or not symptomatic.