Advanced Solid Tumor
Conditions
Brief summary
This is an open-label study in advanced solid tumor patients to determine if entrectinib affects the pharmacokinetics of midazolam and any of its pharmacologically active metabolites.
Interventions
DRUGEntrectinib
600 mg oral capsule (fasted and fed)
2 mg oral syrup (fasted)
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
All patients entering this study will receive midazolam and entrectinib.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must meet the following criteria in order to be included in the research study: 1. Histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumors that are not responsive to standard therapies or for which there is no effective therapy. 2. At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed after prior chemotherapy or small molecule targeted therapy, respectively, at the time of the start of midazolam administration. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1. 4. Adequate hematologic, liver and renal function. 5. Ability to understand the nature of this study and give written informed consent.
Exclusion criteria
Patients who meet any of the following criteria will be excluded from study entry: 1. Participation in another therapeutic clinical trial within 28 days prior to start of midazolam administration. 2. Prior treatment with entrectinib. 3. Known hypersensitivity or intolerance to midazolam or oral formulation excipients, including allergy to cherries. 4. Any condition (in the past 3 months) that may interfere with the conduct of study assessments or may interfere with the interpretation of study results. 5. History of non-pharmacologically induced prolonged QTc interval (e.g., repeated demonstration of a QTc interval \> 500 milliseconds from ECGs). 6. Known active infections that may interfere with the conduct of study assessments or may interfere with the interpretation of study results (bacterial, fungal, or viral, including human immunodeficiency virus positive). 7. Other Protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUClast | 4 weeks | Area under the concentration-time curve from 0 to the last measurable concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib. |
| AUCinf | 4 weeks | Area under the concentration-time curve from 0 to infinity of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib. |
| Cmax | 4 weeks | Peak plasma concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib. |
| Tmax | 4 weeks | Time of maximum concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib. |
| t1/2 | 4 weeks | Terminal half-life of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib. |
Countries
United States
Outcome results
None listed