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

Roche

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Entrectinib; Drug: Midazolam Hydrochloride

Study type: Interventional

Funder types: Industry

Identifiers

NCT03330990

GO40785 (Other Identifier)

RXDX-101-14

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

15 participants in 1 patient group

Entrectinib / Midazolam

Other group

Treatment:

Drug: Midazolam Hydrochloride

Drug: Entrectinib