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

Advanced Solid Tumor Clinical Trial

Official title:

A Phase 1 Study to Evaluate the Potential Pharmacokinetic Interaction Between Entrectinib and Midazolam in Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03330990
• Other study ID #: RXDX-101-14
• Secondary ID: GO40785
• Status: Completed
• Phase: Phase 1
• Start date: November 14, 2017
• Est. completion date: July 11, 2018

Study information

• Verified date: August 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: July 11, 2018
• Est. primary completion date: July 11, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor

Intervention

Drug:
• Entrectinib
600 mg oral capsule (fasted and fed)
• Midazolam Hydrochloride
2 mg oral syrup (fasted)

Locations

Country	Name	City	State
United States	SCRI-Denver Drug Development Program	Denver	Colorado
United States	Tennessee Oncology	Nashville	Tennessee
United States	Florida Cancer Specialists - Sarasota (North Catttlemen Rd)	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Cmax	Peak plasma concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.	4 weeks
Primary	Tmax	Time of maximum concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.	4 weeks
Primary	t1/2	Terminal half-life of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.	4 weeks