A Study of Enzastaurin in Chinese Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma
Condition: Solid Tumor; Lymphoma, Malignant
MeSH terms: Lymphoma
Intervention: Enzastaurin
Intervention description: Administered orally
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the pharmacokinetics (PK) of enzastaurin and its
      metabolites in native Chinese participants with advanced and/or metastatic solid tumors or
      lymphoma. Information about any side effects that may occur will also be collected. Treatment
      of disease is not the main purpose of the study.

      This is a Phase 1 study of enzastaurin in native Chinese participants with advanced and/or
      metastatic solid tumors or lymphoma. Participants will receive daily doses of enzastaurin for
      14 days, stop dosing for 3 days during PK sampling, and resume dosing on Day 18. Participants
      may be allowed to receive enzastaurin for approximately 2 to 4 weeks after day 18 to provide
      an opportunity for a participant's oncologist to assess the potential benefit of the
      participant continuing to receive enzastaurin in the safety extension phase. There is no
      planned duration for the extension phase; participants are allowed to continue receiving
      enzastaurin until disease progression or other reason for discontinuation as per the
      investigator's assessment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have given written informed consent

          -  Have a histologic or cytologic diagnosis of cancer (solid tumor or lymphoma) with
             clinical or radiologic evidence of locally advanced and/or metastatic disease for
             which no life-prolonging therapy exists. (Note: participants with glioblastoma, and
             other hematologic malignancies [except lymphoma] are excluded from this study.)

          -  Male and female participants with reproductive potential must use an approved
             contraceptive method, if appropriate (for example, intrauterine device, birth control
             pills, or barrier device) during and for 3 months after discontinuation of study
             treatment. Women with childbearing potential must have a negative serum pregnancy test
             within 7 days prior to study enrollment.

          -  Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG)
             scale and, in the investigator's opinion, are suitable for participation in the study

          -  Have discontinued all previous therapies for cancer, including chemotherapy,
             radiotherapy, anticancer hormone therapy, or other investigational therapy for at
             least 30 days prior to study entry (6 weeks for mitomycin-C or nitrosoureas), and have
             recovered from the acute effects of therapy

          -  If the participants have hormone-refractory prostate cancer, the study doctor will
             discuss with the participants what drugs they would be allowed to continue to receive
             during the study

          -  Have adequate organ function, including:

               -  Bone Marrow Reserve: absolute neutrophil count (ANC) greater than or equal to 1.5
                  × 10^9/Liter (L) prior to treatment, platelets greater than or equal to 100 ×
                  10^9/L, and hemoglobin greater than or equal to 10 gram/deciliter (g/dL).
                  Participants may receive erythrocyte transfusions to achieve this hemoglobin
                  level at the discretion of the investigator. Participants may be allowed
                  erythropoietin of choice as per standard of care.

               -  Hepatic: bilirubin within 1.5 times the upper limit of normal (ULN), alanine
                  transaminase, and aspartate transaminase less than or equal to 2.5 times ULN or
                  less than or equal to 5 times ULN when liver metastases are known

               -  Renal: serum creatinine less than or equal to 1.5 milligram/deciliter (mg/dL)

          -  Electrolytes: Participants may be entered into the study if, in the investigator's
             opinion, any electrolyte disorders, including potassium less than 3.4
             milliequivalents/liter (mEq/L), calcium less than 8.4 mg/dL, or magnesium less than
             1.2 (mEq/L), may be appropriately managed and stabilized by the time of the laboratory
             evaluation on the lead-in day. If electrolytes have not been stabilized during this
             time, the participant will be discontinued from the study. Participants with
             hypercalcemia are excluded.

          -  Have an estimated life expectancy, in the judgment of the investigator, that will
             permit the participant to complete the PK phase and at least 1 cycle of the safety
             extension phase (if the participant were to participate in the safety extension phase)

        Exclusion Criteria:

          -  Have received treatment within 28 days of the first dose of study drug with an
             experimental agent for non cancer indications that has not received regulatory
             approval for any indication

          -  Participants with glioblastoma or hematologic malignancies other than lymphoma are
             excluded from this study. Participants who have central nervous system (CNS)
             metastases (unless the participant has completed successful local therapy.

        for CNS metastases and has been off of corticosteroids for at least 4 weeks before starting
        study therapy) are excluded. In the absence of a clinical suspicion of brain metastases, no
        screening computed tomography (CT) or magnetic resonance imaging (MRI) scan before
        enrollment is required.

          -  Serious concomitant systemic disorder, including active infection, that is
             incompatible with the study (at the discretion of the investigator)

          -  Have a history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
             infections

          -  Have a serious cardiac condition

          -  Have abnormal electrocardiogram (ECG) findings, at the discretion of the investigator

          -  Use medications that are known to cause certain changes in electrocardiogram (ECG)
             readings

          -  Have a history of unexplained syncope (fainting or passing out) within the last year,
             or have a known family history of unexplained sudden death

          -  Have had a complete gastrectomy or other significant gastrointestinal diseases that,
             in the investigator's opinion, may significantly impact drug absorption

          -  Are receiving total parenteral nutrition

          -  Are not able to swallow tablets

          -  Are a woman who is breast feeding, lactating, or pregnant

          -  Are allergic to enzastaurin

          -  Are receiving herbal regimens

          -  Drugs and herbal supplements that are known to be potent or moderate inhibitors or
             inducers of cytochrome P450 (CYP)3A are specifically excluded. Foods that are known to
             be potent or moderate inhibitors of CYP3A (for example, grapefruit, grapefruit juice,
             Seville oranges, or Seville orange juice) are also specifically excluded during the
             study. In addition, starfruit and starfruit juice are excluded during the PK phase of
             the study.

          -  Drugs with narrow therapeutic windows that are also known substrates of CYP2C9,
             CYP2C8, CYP2C19, and CYP3A are excluded

          -  Have an average weekly alcohol intake that exceeds 21 units per week (men) and 14
             units per week (women) or are unwilling to stop alcohol consumption from the lead-in
             day through the completion of collecting samples for study drug measurement (1 unit =
             12 oz or 360 milliliter (mL) of beer; 5 ounces (oz) or 150 mL of wine; 1.5 oz or 45 mL
             of distilled spirits)

          -  Use of drugs of abuse, as evidenced by history and/or positive findings on urinary
             drug screening, unless prescribed by a physician (for example, narcotic pain
             medication)

          -  The investigator thinks you should not participate for any reason