solid tumor tumor that develops in an organ
Conditions
Interventions
Part A:
Midazolam: 2 single 3 mg doses on Day 1 and Day 21.
Brigatinib: 90 mg QD×7 days, followed by 180 mg QD× 20 days.
Part B: Brigatinib at highest tolerated dose (180, 120, 90, or 60) QD×28 days
Sponsors
ARIAD wholly owned subsidiary of Takeda Pharmaceutical Company Limited
Eligibility
Age
18 Years to 99 Years
Inclusion 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 (<
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Endpoints and Assessments: * Primary: Midazolam PK parameters in the presence and absence of brigatinib, including: * Area under the concentration-time curve from time 0 to infinity (AUC*) * Maximum observed concentration (Cmax) * Time of first occurrence of Cmax (tmax). | — |
Secondary
| Measure | Time frame |
|---|---|
| Primary: Midazolam PK parameters in the presence and absence of brigatinib, including: * Area under the concentration-time curve from time 0 to infinity (AUC*) * Maximum observed concentration (Cmax) * Time of first occurrence of Cmax (tmax). Other endpoints include safety and tolerability. Statistical Considerations: Midazolam PK parameters in the presence and absence of brigatinib will be summarized descriptively. For the estimation of the effect of brigatinib on midazolam PK, the ratios of geometric mean midazolam AUC* and Cmax (with vs without brigatinib coadministration) and the associated 2-sided 90% CIs will be calculated on the basis of the within-patient variance using a mixed-effects analysis of variance. An interim analysis will be conducted after all patients complete Part A of the study. Descriptive statistics will be presented for continuous safety variables (laboratory test values, vital signs, weight) by scheduled time point. Shift tables for laboratory parameters will be generated to show changes in National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, grade from Baseline to the worst post-Baseline value. Sample Size Justification: It is anticipated that approximately 20 patients will be enrolled to obtain approximately 15 PK evaluable patients. The sample size calculation was based on the expected 2-sided 90% CI for the difference in the paired, log-transformed AUC* means of midazolam in the absence and presence of brigatinib. The within-patient coefficient of variation for midazolam AUC* was estimated to be 28% on the basis of a pooled analysis of data from 5 drug-drug interaction studies with midazolam conducted in patients with cancer [1-5]. Assuming that the AUC* ratio for midazolam in the presence versus absence of brigatinib is 1, with a sample size of 15, the 90% CI for the AUC* ratio is expected to be 0.84 to 1.19 on the basis of the variance assumptions. If the AUC* ratio for mi | — |
Countries
Netherlands
Outcome results
None listed