TS-1 in Combination With Calcium Folinate in Patients With Heavily Pre-treated mCRC

Primary Objective: To determine disease control rate (DCR) of TS-1® in patients with heavily pre-treated metastatic colorectal cancer Secondary Objectives: * To determine objective response rate (ORR) * To determine time to progression (TTP) * To determine overall survival (OS) * To assess incidence of adverse events (AEs), serious adverse events (SAEs) \[Safety and Tolerability\]

Sex

All

Minimum age

20 Years

Inclusion Criteria:

1. histologically or cytologically confirmed colorectal adenocarcinoma;
2. metastatic and unresectable disease;
3. presence of at least one measurable tumor lesion which is defined as lesion that can be measured in at least one dimension (longest diameter) with a minimum size of:

   1. 10mm by CT scan and MRI (no less than double the slice thickness and a minimum of 10mm);
   2. 20mm by conventional techniques;
4. previously treatment to

   1. fluoropyrimidine, oxaliplatin and irinotecan;
   2. at least one targeted therapy
5. adequate hematopoietic function which is defined as below:

   1. hemoglobin ≥ 9 g/dL;
   2. absolute neutrophil count (ANC) ≥ 1,500/mm3;
   3. platelet count ≥ 100,000/mm3;
6. adequate hepatic function which is defined as below:

   1. total bilirubin ≤ 2 times upper limit of normal (ULN);
   2. hepatic transaminases (ALT and AST) ≤ 3 x ULN. If there are known liver metastases, ALT or AST must be ≤ 5 x ULN;
7. adequate renal function which is defined as below:

   a. serum creatinine ≤ 1.5 x ULN;
8. age of 20 years or above;
9. ECOG performance status 0-2;
10. life expectancy of at least 12 weeks;
11. ability to take oral medication;
12. ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

1. history or known presence of brain metastasis;
2. presence of mental disease or psychotic manifestation;
3. significant medical conditions that is contraindicated to study medication or render patient at high risk from treatment complications based on investigator's discretion;
4. presence of diarrhea ≥ grade 2 in common terminology criteria for adverse event version 4.0 (CTCAE v4.0);
5. other malignancy within the past 5 years (different site or histology) except for adequately treated basal or squamous cell skin cancer or cervical cancer in situ;
6. recent (within 30 days prior to study treatment) treatment of another investigational drug;
7. pregnant women or nursing mothers, or positive pregnancy test for women of childbearing potential. Patients with childbearing potential should have effective contraception for both the patient and his or her partner during the study.

• BACKGROUNDLee WS, Yun SH, Chun HK, Lee WY, Yun HR, Kim J, Kim K, Shim YM. Pulmonary resection for metastases from colorectal cancer: prognostic factors and survival. Int J Colorectal Dis. 2007 Jun;22(6):699-704. doi: 10.1007/s00384-006-0218-2. Epub 2006 Nov 16. PMID 17109105
• BACKGROUNDVan Cutsem E, Nordlinger B, Adam R, Kohne CH, Pozzo C, Poston G, Ychou M, Rougier P; European Colorectal Metastases Treatment Group. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer. 2006 Sep;42(14):2212-21. doi: 10.1016/j.ejca.2006.04.012. Epub 2006 Aug 10. PMID 16904315
• BACKGROUNDYoo PS, Lopez-Soler RI, Longo WE, Cha CH. Liver resection for metastatic colorectal cancer in the age of neoadjuvant chemotherapy and bevacizumab. Clin Colorectal Cancer. 2006 Sep;6(3):202-7. doi: 10.3816/CCC.2006.n.036. PMID 17026789
• BACKGROUNDAlberts SR, Horvath WL, Sternfeld WC, Goldberg RM, Mahoney MR, Dakhil SR, Levitt R, Rowland K, Nair S, Sargent DJ, Donohue JH. Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study. J Clin Oncol. 2005 Dec 20;23(36):9243-9. doi: 10.1200/JCO.2005.07.740. Epub 2005 Oct 17. PMID 16230673
• BACKGROUNDDawood O, Mahadevan A, Goodman KA. Stereotactic body radiation therapy for liver metastases. Eur J Cancer. 2009 Nov;45(17):2947-59. doi: 10.1016/j.ejca.2009.08.011. Epub 2009 Sep 19. PMID 19773153
• BACKGROUNDKemeny N. Management of liver metastases from colorectal cancer. Oncology (Williston Park). 2006 Sep;20(10):1161-76, 1179; discussion 1179-80, 1185-6. PMID 17024869
• BACKGROUNDMuratore A, Zorzi D, Bouzari H, Amisano M, Massucco P, Sperti E, Capussotti L. Asymptomatic colorectal cancer with un-resectable liver metastases: immediate colorectal resection or up-front systemic chemotherapy? Ann Surg Oncol. 2007 Feb;14(2):766-70. doi: 10.1245/s10434-006-9146-1. Epub 2006 Nov 14.