Phase 2a Study to Evaluate Suppression of Methotrexate-induced Mucositis by TK112690
Condition: Mucositis
MeSH terms: Mucositis
Intervention: TK-112690; Placebo TK-112690
Intervention description: TK112690 treatment pre-methotrexate treatment; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A total of 22 patients will be enrolled into one of 2 different: TK112690 treated or placebo treated.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: The study will be partially blinded. The patient and investigator will be blinded as to whether TK112690 or placebo is administered. The clinical research organization, sponsor, and site pharmacist will know whether the patient was administered active drug or placebo.
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Mucositis; Methotrexate; Uridine Phosphorylase Inhibitor; Head and Neck Cancer

Summary:

      Patients will receive methotrexate at a dose of 45 mg/m2 administered weekly for 4
      consecutive weeks as an iv infusion along with a nutritional supplement administered two
      hours before the methotrexate. One hour before the methotrexate treatment the patients will
      be administered the first infusion of the day of either TK112690 or placebo depending on
      randomization. Five hours after the methotrexate treatment the patients will be administered
      the second treatment of either TK112690 or placebo depending on randomization. The TK112690
      dose will be 45 mg/kg.
    

Eligibility criteria:

        Inclusion Criteria

          -  Male and female subjects over 18 years old with a histologically or cytological
             confirmed diagnosis of locally residual, recurrent or metastatic SCCHN.

          -  Subject must have failed at least one courses of non-MTX chemotherapy, or one course
             of non-MTX chemotherapy and chemo radiation for treating their SCCHN.

          -  No prior systemic treatments for cancer (chemotherapy and/or radiotherapy) 4 weeks
             prior to screening.

          -  No other concurrent, active, invasive malignancies.

          -  An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          -  Must have a life expectancy of at least 6 months.

          -  History of brain metastases allowed if disease has stabilized or improved after
             radiation and/or craniotomy.

          -  No active angina or uncontrolled arrhythmia.

          -  No detectable infection including hepatitis B/C and HIV.

          -  Not pregnant or nursing. Women of childbearing potential must have a negative urine
             pregnancy test at screening and on the day before dosing and must use medically
             acceptable methods of birth control. Acceptable methods of birth control include oral
             or transdermal contraceptives, condoms, spermicidal foam, IUD, progestin implant or
             injection, abstinence, vaginal ring, or sterilization of partner. The reason for
             non-childbearing potential, such as bilateral tubal ligation, bilateral oophorectomy,
             hysterectomy, or post-menopausal for ≥ 1 year, must be specified in the patient's
             medical history file and CRF.

          -  Must have adequate organ and immune function as indicated by the following laboratory
             values:

        Parameter Laboratory Values Serum creatinine ≤1.5 x ULN Est. creatinine clearance ≥45
        mL/min Total bilirubin ≤2.0 mg/dL (≤34.2 μmol/L) AST & ALT ≤3 x ULN Absolute granulocytes
        ≥1.5 x 109 cells/L Platelets ≥100,000/µL

        ● Be able to read and understand, and provide a signature or thumb impression on the
        Informed Consent Form (ICF) before entering the study.

        Exclusion Criteria:

          -  Subject has not failed at least one courses of non-MTX chemotherapy or one course of
             non-MTX chemotherapy and chemo radiation for treating their SCCHN.

          -  Uncontrolled active infection.

          -  Current mucositis (>Grade 1).

          -  Pregnant or nursing mother.

          -  Prior history of a cerebrovascular accident or hemorrhage.

          -  Congestive heart failure, as defined by New York Heart Association class III or IV.

          -  Uncontrolled hypertension.

          -  Active psychiatric/mental illness making informed consent or useful clinical follow-up
             unlikely.

          -  Subjects who have previously been enrolled into this study and subsequently withdrew.

          -  Subject receiving other investigational agent(s).

          -  Any systemic immunosuppressive medication/therapy (eg, other chemotherapy, steroids).

          -  Any significant systemic illness, unstable or severe medical condition(s) that could
             put the subject at risk during the study, interfere with outcome measures, or affect
             compliance with the protocol procedures such as intercurrent infection and/or
             autoimmune disease, ie, any condition that compromises the immune system.

          -  Known or suspected intolerance or hypersensitivity to the study materials (TK-112690
             and/or excipients or closely related compounds).

          -  Subjects, who have received, or plan to receive, radiation or chemotherapy within 4
             weeks of screening.

          -  Subjects that have a history of poor compliance in clinical research studies.

          -  Subjects that have participated in any other investigative clinical trial in the past
             4 weeks.