A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate, Midazolam, in Participants With ALK-Positive or ROS1-Positive Solid Tumors
Condition: Carcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors
MeSH terms: Neoplasms
Intervention: Midazolam; Brigatinib
Intervention description: Midazolam syrup.; Brigatinib tablets.
Intervention MeSH terms: Midazolam
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy, brigatinib, lung cancer, ALK, ROS1

Summary:

      The purpose of this study is to characterize the effect of repeat-dose administration of
      brigatinib 180 milligram (mg) once daily (QD) on the single-dose pharmacokinetics (PK) of
      midazolam.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Locally advanced or metastatic solid tumors who meet 1 of the following 4 criteria:

               -  With locally advanced or metastatic ALK-positive NSCLC who have progressed on or
                  are intolerant to treatment with at least 1 other ALK inhibitor.

               -  With ALK-positive nonlung solid tumors that are locally advanced or metastatic
                  and for whom no standard, nonexperimental therapy is available.

               -  With locally advanced or metastatic ROS1-positive NSCLC who have progressed on
                  crizotinib therapy or are intolerant to crizotinib, or

               -  With ROS1-positive nonlung solid tumors that are locally advanced or metastatic
                  and for whom no standard, nonexperimental therapy is available.

          2. Eastern cooperative Oncology Group (ECOG) performance status of 0 or 1.

          3. Have at least 1 target lesion per response evaluation criteria in solid tumors
             (RECIST) version 1.1.

          4. Have recovered from toxicities related to prior anticancer therapy to National Cancer
             Institute common terminology criteria for adverse events (NCI CTCAE) version 4.03
             Grade less than or equal to (<=) 1.

          5. Suitable venous access for study-required blood sampling (that is, including PK and
             laboratory safety tests).

        Exclusion Criteria:

          1. Systemic treatment with strong or moderate cytochrome P450 3A (CYP3A) inhibitors or
             inducers within 14 days before enrollment.

          2. Prior therapy with brigatinib.

          3. Received prior ALK-inhibitor therapy within 7 days before the first dose of study
             drug.

          4. Treatment with any investigational systemic anticancer agents within 14 days or 5
             half-lives, whichever is longer, before the first dose of study drug.

          5. Received chemotherapy or radiation therapy within 14 days before the first dose of
             study drug, except for stereotactic radiosurgery (SRS) or stereotactic body radiation
             therapy.

          6. Received antineoplastic monoclonal antibodies within 30 days before the first dose of
             study drug.

          7. Had major surgery within 30 days before the first dose of study drug. Minor surgical
             procedures, such as catheter placement or minimally invasive biopsies, are allowed.

          8. Have current spinal cord compression (symptomatic or asymptomatic and detected by
             radiographic imaging). Patients with leptomeningeal disease and without cord
             compression are allowed.