Clinical trial NCT03330990: Evaluate the Effect of Entrectinib on the Pharmacokinetics of Midazolam in Cancer Patients
Official title: A Phase 1 Study to Evaluate the Potential Pharmacokinetic Interaction Between Entrectinib and Midazolam in Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-11-06
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All patients entering this study will receive midazolam and entrectinib.
Primary purpose: OTHER

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.


Eligibility criteria: 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/Exclusion criteria apply.

Primary outcomes:
measure: AUClast
timeFrame: 4 weeks
measure: AUCinf
timeFrame: 4 weeks
measure: Cmax
timeFrame: 4 weeks
measure: Tmax
timeFrame: 4 weeks
measure: t1/2
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Denver
country: United States
facility: SCRI-Denver Drug Development Program
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists - Sarasota (North Catttlemen Rd)
state: Florida
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: