Study of CS-7017 in Colorectal Cancer Patients Who Have Achieved Disease Control Following First-Line Chemotherapy

A Randomized, Double-Blind Placebo-Controlled Phase 2 Study of CS-7017 in Colorectal Cancer Patients Who Have Achieved Disease Control Following First-Line Chemotherapy

Monotherapy treatment with CS-7017 to assess progression-free-survival (PFS) of subjects who achieved an objective response of Disease Control on first line therapy with Folinic acid (leucovorin), Fluorouracil (5-FU), Oxaliplatin (Eloxatin) known as FOLFOX; or Folinic acid (leucovorin), Fluorouracil (5-FU), irinotecan (Camptosar) known as FOLFIRI.

Inclusion Criteria:

• Patients with histologically confirmed, metastatic CRC that have achieved confirmed maximal benefit of DC following treatment with standard first line chemotherapy of a 5-fluoropyrimidine plus either oxaliplatin or irinotecan. Patients should be entered onto this trial within 8 weeks of completing first line therapy;

• If CR was not achieved: measurable disease, i.e. at minimum one unidimensionally-measurable target lesion according to RECIST (Response Evaluation Criteria in Solid Tumors);

• Age >= 18 years and Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 at study entry;

• Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, Version 3.0, grade =< 1;

• Adequate organ and bone marrow function as evidenced by:

  • Haemoglobin >= 10 g/dL (transfusion and/or growth factor support allowed);
  • Absolute neutrophil count (ANC) >= 1.5 x 109/L;
  • Platelet count >= 100 x 109/L;
  • Serum creatinine =< 1.5 x ULN or creatinine clearance >60 mL/min;
  • AST and alkaline phosphatase <2.5 x ULN if without liver metastasis and =< 5.0 x ULN if liver metastasis;
  • Total bilirubin =< 2.0 x ULN;
  • Prothrombin time (PT)/International Normalised Ratio (INR) within normal limits (WNL) unless therapeutically anticoagulated;

• Women of childbearing potential and men must be willing to consent to using highly effective methods of contraception (eg, hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device) while on treatment and for at least 3 months thereafter;

• Males with the potential to father children must use two of the following methods of contraception acceptable for the study (e.g. hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device) while on trial treatment and for at least 3 months thereafter.

• All female subjects of childbearing potential must have a negative pregnancy test (plasma or urine) result within 7 days before initiating study treatment;

• Baseline laboratory tests and tumor assessments must have been performed within 2 weeks before initiating study treatment;

• Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an IEC-approved ICF before performance of any study specific procedures or tests.

Exclusion Criteria:

• Anticipation of need for a major surgical procedure or RT during the study;
• Treatment with chemotherapy, hormonal therapy, minor surgery, or any investigational agent within 4 weeks before study enrolment. Treatment with immunotherapy, biological therapy, or major surgery within 6 weeks before study enrolment. Treatment with RT within 1 week before study enrolment.
• History of any of the following conditions: diabetes mellitus requiring treatment with insulin or oral agents;
• Concomitant use of other TZDs;
• Myocardial infarction with significant impairment of cardiac function (e.g., ejection fraction =< 50%); severe/unstable angina pectoris; coronary/peripheral artery bypass graft; congestive heart failure; cerebrovascular accident (CVA) or transient ischemic attack (TIA), pulmonary embolism, or other clinically significant thromboembolic event; clinically significant pulmonary disease (e.g., severe chronic obstructive pulmonary disease [COPD] or asthma);
• Brain metastasis; an uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis;
• Pleural or pericardial effusion. Subjects with minimal pleural effusion may be eligible upon request by Investigator and approval by Sponsor;
• Clinically significant active infection that requires antibiotic therapy or Human Immunodeficiency Virus (HIV) positive subjects receiving antiretroviral therapy;
• Pregnant or breast feeding;
• Known history of severe hypersensitivity reactions to any of the components of CS 7017 formulations;
• Serious intercurrent medical or psychiatric illnesses or any other conditions that in the opinion of the Investigator would impair the ability to give informed consent or unacceptably reduce protocol compliance or safety of the study treatment;