A Drug Interaction Study of Tasisulam in Patients With Advanced Cancer or Lymphoma
Condition: Lymphoma; Advanced Cancer
MeSH terms: Lymphoma
Intervention: Tolbutamide; Tasisulam
Intervention description: Administered orally; Administered intravenously
Intervention MeSH terms: Tolbutamide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced or Metastatic Solid Tumors or Lymphoma

Summary:

      The purpose of this study was to assess the effect of tasisulam as an inhibitor of CYP2C9,
      using tolbutamide as a probe substrate. This study was to have 3 treatment periods, and
      continued access in an extension period. Period 1 is 4 days in length. Periods 2 and 3 are
      each approximately 28 days in length. Due to the early termination of the trial, only 1
      Period 3 participant enrolled in the extension period before study termination.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have histologically or cytologically confirmed solid malignancy or lymphoma that is
             advanced and/or metastatic disease which has not responded to standard therapy or for
             which no standard therapy exists.

          2. Have given written informed consent prior to any study-specific procedures.

          3. Have a performance status of less than or equal to 1 on the Eastern Cooperative
             Oncology Group (ECOG) scale and an estimated life expectancy of greater than 12 weeks.

          4. Have discontinued all previous therapies for cancer, including chemotherapy,
             radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at
             least 30 days (45 days for mitomycin-C or nitrosoureas) prior to study enrollment and
             recovered from the acute effects of therapy. Limited field radiotherapy is permitted
             (in consultation with the investigator).

          5. Have adequate organ function.

          6. Are reliable and willing to make themselves available for the duration of the study
             and are willing to follow study procedures.

          7. Males and females with reproductive potential must agree to use medically approved
             contraceptive precautions during the trial and for 6 months following the last dose of
             study drug.

          8. Females with child-bearing potential must have had a negative serum pregnancy test
             less than 7 days prior to the first dose of study drug.

        Exclusion Criteria:

          1. Have received treatment within 30 days of the initial dose of study drug with an
             experimental agent for noncancer indications that has not received regulatory approval
             for any indication.

          2. Have known allergies to tasisulam or related compounds.

          3. Have serious preexisting medical conditions.

          4. Show evidence of significant active neuropsychiatric disease or central nervous system
             (CNS) disease (for example, Alzheimer's disease or Parkinson's disease). Patients with
             active brain metastasis are excluded.

          5. Have current acute or chronic leukemia.

          6. Females who are pregnant or lactating.

          7. Have known positive test results in human immunodeficiency virus (HIV), hepatitis B
             surface antigen (HBSAg), or hepatitis C antibodies (HCAb).

          8. History of severe allergies or multiple adverse drug reactions.

          9. Are persons who have previously completed or withdrawn from this study or any other
             study investigating tasisulam.

         10. Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the
             investigator, increases the risks associated with participating in the study.

         11. Serious concomitant systemic disorder, including diabetes or active infection,
             incompatible with the study.

         12. Clinically significant cardiac symptomology.

         13. Patients being treated with warfarin.

         14. Patients being treated with sulfonylureas

         15. Regularly use drugs of abuse and/or show positive findings on urinary drug screening
             that is not in accordance with known/acceptable concomitant medication.

         16. Patients who have received medications that are known inducers or inhibitors of CYP2C9
             within 30 days prior to enrollment.

         17. Have donated or lost blood of more than 500 milliliter (mL) within the last month.

         18. Have an average weekly alcohol intake that exceeds 21 units per week (males up to age
             65) and 14 units per week (males over 65 and females) (1 unit = 12 ounces (oz) or 360
             mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).

         19. Failure for any reason to satisfy the investigator for adequate fitness to participate
             in the study.

         20. Screening albumin levels less than 30 grams/Liter (g/L).