Evaluate the Effect of Entrectinib on the Pharmacokinetics of Midazolam in Cancer Patients

Phase 1

Completed

• Conditions: Advanced Solid Tumor
• Interventions: Drug: Entrectinib; Drug: Midazolam Hydrochloride

• Registration Number: NCT03330990
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-10-27
• Study First Submitted QC: 2017-10-31
• Study First Posted: 2017-11-06
• Study Start: 2017-11-14
• Primary Completion: 2018-07-11
• Study Completion: 2018-07-11
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-17
• Last Update Posted: 2018-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Entrectinib / Midazolam	Midazolam Hydrochloride	-
Entrectinib / Midazolam	Entrectinib	-

Primary Outcome Measures

Name	Time	Method
Cmax	4 weeks	Peak plasma 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.
t1/2	4 weeks	Terminal half-life of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.
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.
Tmax	4 weeks	Time of maximum concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.

Trial Locations

Locations (3)

SCRI-Denver Drug Development Program; 🇺🇸 Denver, Colorado, United States

Florida Cancer Specialists - Sarasota (North Catttlemen Rd); 🇺🇸 Sarasota, Florida, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States