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

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ClinicalTrials.gov Identifier: NCT03330990
Recruitment Status : Completed
First Posted : November 6, 2017
Last Update Posted : August 21, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: Entrectinib Drug: Midazolam Hydrochloride Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Intervention Model Description: 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 : November 14, 2017
Actual Primary Completion Date : July 11, 2018
Actual Study Completion Date : July 11, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Entrectinib / Midazolam Drug: Entrectinib
600 mg oral capsule (fasted and fed)

Drug: Midazolam Hydrochloride
2 mg oral syrup (fasted)




Primary Outcome Measures :
  1. AUClast [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 4 weeks ]
    Peak plasma concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.

  4. Tmax [ Time Frame: 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 [ Time Frame: 4 weeks ]
    Terminal half-life of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03330990


Locations
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United States, Colorado
SCRI-Denver Drug Development Program
Denver, Colorado, United States, 80218
United States, Florida
Florida Cancer Specialists - Sarasota (North Catttlemen Rd)
Sarasota, Florida, United States, 34232
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03330990     History of Changes
Other Study ID Numbers: RXDX-101-14
GO40785 ( Other Identifier: Hoffman-La Roche )
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: August 21, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Midazolam
Entrectinib
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors