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

NCT03330990 | Completed Phase 1 FDA Drug

• 2 other identifiers: RXDX-101-14GO40785
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (5)

• AUClast

  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.

  4 weeks

• AUCinf

  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.

  4 weeks

• Cmax

  Peak plasma concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.

  4 weeks

• Tmax

  Time of maximum concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.

  4 weeks

• t1/2

  Terminal half-life of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.

  4 weeks

Study Arms (1)

Entrectinib / Midazolam

OTHER

Drug: Entrectinib; Drug: Midazolam Hydrochloride

Interventions

Entrectinib DRUG

600 mg oral capsule (fasted and fed)

Entrectinib / Midazolam

Midazolam Hydrochloride DRUG

2 mg oral syrup (fasted)

Entrectinib / Midazolam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria in order to be included in the research study:
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1.
• Adequate hematologic, liver and renal function.
• Ability to understand the nature of this study and give written informed consent.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Participation in another therapeutic clinical trial within 28 days prior to start of midazolam administration.
• Prior treatment with entrectinib.
• Known hypersensitivity or intolerance to midazolam or oral formulation excipients, including allergy to cherries.
• 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.
• History of non-pharmacologically induced prolonged QTc interval (e.g., repeated demonstration of a QTc interval \> 500 milliseconds from ECGs).
• 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).

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (3)

SCRI-Denver Drug Development Program

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists - Sarasota (North Catttlemen Rd)

Sarasota, Florida, 34232, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Interventions

entrectinib; Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All patients entering this study will receive midazolam and entrectinib.

Study Record Dates

• First Submitted: October 27, 2017
• First Posted: November 6, 2017
• Study Start: November 14, 2017
• Primary Completion: July 11, 2018
• Study Completion: July 11, 2018
• Last Updated: August 21, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)