Pemetrexed and Erlotinib for Metastatic Colorectal Cancer

Inclusion Criteria:

1. Male or female, aged ≥ 19 years
2. Histologic or cytologic confirmed diagnosis of colorectal carcinoma with metastatic (STAGE IV) disease.
3. Confirmed KRAS(codon 12 or 13) status
4. Prior chemotherapy for metastatic disease is required; prior regimens must include fluoropyrimidine, oxaliplatin and irinotecan
5. Eastern Cooperative Oncology Group performance status ≤ 2
6. Patients who can swallow oral medication.
7. Life expectancy of greater than 3 months
8. Patients must have normal organ and marrow function as defined below:

   * absolute neutrophil count ≥ 1,500/mm3
   * hemoglobin ≥ 9 g/dl
   * platelets ≥ 100,000/mm3
   * serum total bilirubin ≤ 1.5 X institutional upper limit of normal
   * aspartate aminotransferase(SGOT)/alanine aminotransferase(SGPT) ≤ 3.0 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 or Creatinine Clearance ≥ 50ml/min
9. The effects of Pemetrexed and Erlotinib 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 6 months thereafter. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
10. 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. Previous treatment with Pemetrexed and Erlotinib
2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pemetrexed or Erlotinib or other agents used in the study
3. Patients who can not allow the administration of Folic acid or Vitamin B12.
4. 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.
5. Systemic chemotherapy within three weeks after the administration of the last before the test treatment
6. Major surgical operation or major trauma within 4 weeks.
7. Patients who have had wide-ranged radiotherapy within 4 weeks or limited radiotherapy within 2 2 weeks.
8. Persistent toxicity (\> CTCAE grade 1) related to previous treatment except for the hair loss.
9. 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.
10. 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.
11. Breast-feeding or pregnant female