Study of CS-7017 in Combination With FOLFIRI in Subjects With Metastatic Colorectal Cancer Who Failed First-Line Therapy
Condition: Colorectal Cancer; Neoplasms, Colorectal
MeSH terms: Colorectal Neoplasms
Intervention: CS7017; irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)
Intervention description: CS-7017 (0.25mg tablet) Two CS-7017 tablets will be administered by mouth (PO) BID every 12 hours. FOLFIRI will be administered IV once every 2 weeks.; FOLFIRI will be administered IV once every 2 weeks.
The FOLFIRI regimen consists of:
Irinotecan, 180 mg/m^2 IV infusion over 30 to 120 minutes
Leucovorin, 400 mg/m^2 IV infusion to match the duration of the irinotecan infusion
5-FU, 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours continuous infusion)
Intervention MeSH terms: Leucovorin; Fluorouracil; Irinotecan; Efatutazone; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic; colon; rectum; combination; chemotherapy

Summary:

      This phase 2, randomized, active-controlled, open-label, parallel group, multicenter study
      will be conducted at up to 18 study centers in the US, Central America, and South America.
      Adult subjects with metastatic colorectal cancer (CRC) who failed first-line chemotherapy
      will participate in the study, which will be conducted on an outpatient basis. It is
      anticipated that 100 subjects will be enrolled to obtain approximately 90 evaluable subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Metastatic CRC that has progressed following first-line therapy.

          -  Measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST], Version
             1.0.

          -  Male or female ≥ 18 years of age.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

          -  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:

               -  Hemoglobin ≥ 9 g/dL (transfusion and/or growth factor support allowed)

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

               -  Platelet count ≥ 100 x 10^9/L

               -  Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) or creatinine clearance
                  ≥ 60 mL/min

               -  Aspartate aminotransferase (AST) and alkaline phosphatase ≤ 2.5 x ULN in
                  participants with no liver metastasis and ≤ 5.0 x ULN in participants with liver
                  metastasis

               -  Total bilirubin ≤ 1.5 x ULN

          -  Women of childbearing potential must be willing to consent to using effective
             contraception (eg, hormonal contraceptives, bilateral tubal ligation, barrier with
             spermicide, intrauterine device) while on treatment and for at least 3 months
             thereafter. Men who are the partner of a woman of childbearing potential must be
             willing to consent to using effective contraception (eg, vasectomy or barrier with
             spermicide) while on treatment and for 3 months thereafter.

          -  All female participants of childbearing potential must have a negative pregnancy test
             (serum or urine) result before initiating study treatment.

          -  Participants 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 Independent Ethics Committee (IEC)- or Institutional Review Board
             (IRB)-approved informed consent form (ICF) (including HIPAA authorization, if
             applicable) before performance of any study-specific procedures or tests.

          -  Participants must be willing and able to comply with scheduled visits, treatment plan,
             laboratory tests, and other study procedures.

        Exclusion Criteria:

          -  First-line treatment with an irinotecan-based regimen (eg, FOLFIRI).

          -  Anticipation of need for a major surgical procedure or radiation therapy (RT) during
             the study.

          -  Treatment with chemotherapy, other thiazolidinediones (TZD), RT, surgery,
             immunotherapy, biological therapy, or any investigational anticancer agent within 4
             weeks before start of study treatment.

          -  History of any of the following conditions within 6 months before initiating study
             treatment:

               -  Diabetes mellitus requiring treatment with insulin or TZD agents

               -  Myocardial infarction with significant impairment of cardiac function (eg,
                  ejection fraction ≤ 50%)

               -  Severe/unstable angina pectoris

               -  Coronary/peripheral artery bypass graft

               -  New York Heart Association (NYHA) class III or IV congestive heart failure

               -  Malabsorption syndrome, chronic diarrhea (lasting > 4 weeks), inflammatory bowel
                  disease, or partial bowel obstruction.

          -  Participants with clinically active brain metastases (defined as untreated,
             symptomatic, or requiring therapy with steroids or anticonvulsants to control
             associated symptoms); uncontrolled seizure disorder; spinal cord compression; or
             carcinomatous meningitis. Participants with treated brain metastasis will be included
             in the study if they have recovered from the acute, toxic effects of RT. A minimum of
             15 days must have elapsed between the end of RT and enrollment into the study.

          -  History of malignancy other than CRC, unless there is an expectation that the
             malignancy has been cured, and tumor-specific treatment for the malignancy has not
             been administered within the previous 5 years.

          -  Clinically significant, severe, active infection requiring IV antibiotic or antiviral
             agents.

          -  Pericardial or pleural effusion (eg, requiring drainage) or pericardial involvement
             with the tumor. Participants with minimal pleural effusion may be eligible upon
             request by Investigator and approval by Sponsor.

          -  Need for concomitant use of other TZD agents during the study.

          -  Previous administration of CS-7017.

          -  Pregnant or breast feeding.

          -  Known to be homozygous for the UGT1A1*28 allele.

          -  Known history of severe hypersensitivity reactions to any of the components of
             CS-7017, irinotecan, leucovorin, or 5-FU.

          -  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.