Advanced Solid TumorPhase 1NCT03330990

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

A Phase 1 study testing Entrectinib and Midazolam Hydrochloride in people with Advanced Solid Tumor, run by Hoffmann-La Roche at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Solid Tumor
What is being tested?: Entrectinib and Midazolam Hydrochloride
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 3 sitesUnited States
Study dates: 14 Nov 2017to 11 Jul 2018
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).
Other Protocol defined Inclusion/Exclusion criteria apply.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

SCRI-Denver Drug Development Program
Denver, Colorado, 80218
Tennessee Oncology
Nashville, Tennessee, 37203
Florida Cancer Specialists - Sarasota (North Catttlemen Rd)
Sarasota, Florida, 34232

Other trials in United States

About this study

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

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
Being tested: Entrectinib, Midazolam Hydrochloride

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EntrectinibDrug
600 mg oral capsule (fasted and fed)
Midazolam HydrochlorideDrug
2 mg oral syrup (fasted)

Study groups in NCT03330990
Study group	Role	What they receive
Entrectinib / Midazolam	Other	Not described Receives: Drug: Entrectinib; Drug: Midazolam Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 4 weeks
Cmax
Peak plasma concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.
Measured: 4 weeks
Tmax
Time of maximum concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.
Measured: 4 weeks
t1/2
Terminal half-life of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.
Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Nov 201711 Jul 2018

First posted6 Nov 2017
Study start14 Nov 2017
Primary completion11 Jul 2018
Study completion11 Jul 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Model description: All patients entering this study will receive midazolam and entrectinib.
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03330990
Sponsor's protocol ID: RXDX-101-14
Other IDs: GO40785
Status last verified: Aug 2018
First submitted: 27 Oct 2017
Last updated: 21 Aug 2018
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

All Advanced Solid Tumor trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Study to Evaluate the Potential Pharmacokinetic Interaction Between Entrectinib and Midazolam in Cancer Patients
ClinicalTrials.gov ID: NCT03330990
Acronym / sponsor ID: RXDX-101-14
Conditions: Advanced Solid Tumor
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: 14 Nov 2017 (actual)
Primary completion: 11 Jul 2018 (actual)
Study completion: 11 Jul 2018 (actual)
First posted: 6 Nov 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: All patients entering this study will receive midazolam and entrectinib.

Arm	Type	Receives
Entrectinib / Midazolam	Other	Drug: Entrectinib, Drug: Midazolam Hydrochloride

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (8 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Entrectinib600 mg oral capsule (fasted and fed)	Drug	Entrectinib / Midazolam
Midazolam Hydrochloride2 mg oral syrup (fasted)	Drug	Entrectinib / Midazolam

Primary outcome

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.
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.
Cmax
Time frame: 4 weeks
Peak plasma concentration of midazolam and the pharmacologically active metabolite 1-hydoxymidazolam in the absence or presence of entrectinib.
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.
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.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2018.
Individual participant dataSharing planned: No

Related trials for Advanced Solid Tumor

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Entrectinib and Midazolam Hydrochloride in people with Advanced Solid Tumor, run by Hoffmann-La Roche at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUClast (time frame: 4 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03330990.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2018.