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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03330990
• Collaborator: (none)
• Enrollment: 15
• Locations: 3
• Arm: 1
• Actual Duration (Months): 7.9
• Patients Per Site: 5
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor	Drug: Entrectinib; Drug: Midazolam Hydrochloride	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: All patients entering this study will receive midazolam and entrectinib.All patients entering this study will receive midazolam and entrectinib.
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 1 Study to Evaluate the Potential Pharmacokinetic Interaction Between Entrectinib and Midazolam in Cancer Patients
• Actual Study Start Date: Nov 14, 2017
• Actual Primary Completion Date: Jul 11, 2018
• Actual Study Completion Date: Jul 11, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Entrectinib / Midazolam	Drug: Entrectinib; 600 mg oral capsule (fasted and fed); Drug: Midazolam Hydrochloride; 2 mg oral syrup (fasted)

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. Cmax [4 weeks]

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

4. Tmax [4 weeks]

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

5. t1/2 [4 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SCRI-Denver Drug Development Program	Denver	Colorado	United States	80218
2	Florida Cancer Specialists - Sarasota (North Catttlemen Rd)	Sarasota	Florida	United States	34232
3	Tennessee Oncology	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03330990
• Other Study ID Numbers: RXDX-101-14; GO40785
• First Posted: Nov 6, 2017
• Last Update Posted: Aug 21, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Midazolam; Entrectinib

Study Results

No Results Posted as of Aug 21, 2018