Solid TumorPhase 1NCT03961100

A Performance and Bioavailability Study of Entrectinib in Healthy Volunteers.

A Phase 1 study testing Entrectinib 600 mg (T1), Entrectinib 600 mg (T2) and Entrectinib 200 mg (R) in people with Solid Tumor, run by Genentech, Inc. at 1 site in United Kingdom.

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 study will evaluate the bioavailability, palatability, safety and tolerability of entrectinib in healthy volunteers. Part 1 of the study will explore the performance of entrectinib multi-particle formulation. Part 2 will evaluate the effect of drug substance particle size on entrectinib bioavailability. Read more about this study

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Solid Tumor
What is being tested?: Entrectinib 600 mg (T1), Entrectinib 600 mg (T2) and Entrectinib 200 mg (R)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: 1 siteUnited Kingdom
Study dates: 6 Jun 2019to 9 Aug 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

A body mass index (BMI) between 18.0 and 32.0 kilogram per square meter (kg/m2), inclusive, and weighing >/=50 kg.
Agreement to comply with measures to prevent pregnancy and restrictions on egg and sperm donation

Who cannot join

Women of childbearing potential, women who are pregnant or breastfeeding, or intending to become pregnant during the study or within 14 days after the final dose of entrectinib or have a pregnant partner
A clinical significant medical history of gastrointestinal surgery (e.g., gastric bypass) or other gastrointestinal disorder (e.g., malabsorption syndrome) that might affect absorption of medicines from the gastrointestinal tract
Presence of a clinically significant disease, illness, medical condition or disorder, or any other medical history determined by the investigator to be clinically significant and relevant
Clinically significant change in health status, or any major illness, or clinically significant acute infection or febrile illness
Use of moderate or potent inhibitors or inducers of CYP P450 3A4 enzyme or P-gp transporter, or use of other prohibited medications
Participation in any other clinical study involving an investigational medicinal product (IMP) or device

Show all 9Show fewer

A positive test result for hepatitis B, hepatitis C (HCV), or human immunodeficiency virus (HIV)
Current smokers and those who have smoked, or users of e-cigarettes and nicotine replacement products within the last 12 months
Known history of clinically significant hypersensitivity, or severe allergic reaction, to entrectinib or related compounds

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Quotient Clinical Ltd, Clinical Research Unit
Nottingham, NG11 6JS

Other trials in United Kingdom

About this study

Official title: A Randomized, Open-Label, Two Part Study to Explore the Performance of Entrectinib Prototype Mini-Tablet Formulations and the Effect of Drug Substance Particle Size On Entrectinib Bioavailability in Healthy Volunteers

Conditions: Solid Tumor
Being tested: Entrectinib 600 mg (T1), Entrectinib 600 mg (T2), Entrectinib 200 mg (R), Entrectinib 200 mg (T)

What participants receive

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

Entrectinib 600 mg (T1)Drug
Test formulation 1 (T1): Multi-particulate formulation 1: entrectinib film-coated mini-tablets
Entrectinib 600 mg (T2)Drug
Test formulation 2 (T2): Multi-particulate formulation 2: entrectinib film-coated mini-tablets
Entrectinib 200 mg (R)Drug
Reference formulation (R): entrectinib hard capsules
Entrectinib 200 mg (T)Drug
Test formulation (T): entrectinib HPMC capsules

Study groups in NCT03961100
Study group	Role	What they receive
Part 1	Experimental	Participants will be randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants will cross-over to three periods taking different formulations of entrectinib. Entrectinib will be administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule. Receives: Drug: Entrectinib 600 mg (T1); Drug: Entrectinib 600 mg (T2); Drug: Entrectinib 200 mg (R)
Part 2	Experimental	Participants will be randomly assigned to one of the two treatment sequences (TR, RT). In each treatment sequences, participants will cross-over to two periods taking different formulations of entrectinib. Entrectinib will be administered as a single 200 mg oral dose under fasted condition in two different formulations. Test formulation (T): hydroxypropyl methylcellulose (HPMC) capsule; Reference formulation (R): hard capsule. Receives: Drug: Entrectinib 200 mg (R); Drug: Entrectinib 200 mg (T)

What is being measured

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

Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Entrectinib
Measured: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
AUC0-inf of Entrectinib Active Metabolite M5
Measured: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
Maximum Plasma Concentration (Cmax) of Entrectinib
Measured: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
Cmax of Entrectinib Active Metabolite M5
Measured: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)

Secondary outcomes (1)

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Treatment-emergent adverse events (TEAEs) are AEs that were not present before the first dose of study drug or that were present before the first dose of study drug but worsened in intensity during exposure to study drug.
Measured: From Day -1 to Day 5 of each periods (each period=7 days)

Timeline

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

6 Jun 20199 Aug 2019

First posted23 May 2019
Study start6 Jun 2019
Primary completion9 Aug 2019
Study completion9 Aug 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Solid TumorStudies of the same condition, open and under way.
More trials run by Genentech, Inc.The 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: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03961100
Sponsor's protocol ID: GP41341
Other IDs: 2019-000783-15, 2019
Status last verified: Sep 2020
First submitted: 22 May 2019
Last updated: 7 Sep 2020
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).

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
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

All Solid Tumor trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Open-Label, Two Part Study to Explore the Performance of Entrectinib Prototype Mini-Tablet Formulations and the Effect of Drug Substance Particle Size On Entrectinib Bioavailability in Healthy Volunteers
ClinicalTrials.gov ID: NCT03961100
Acronym / sponsor ID: GP41341
Conditions: Solid Tumor
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Genentech, Inc.Industry (pharma, biotech, devices)
Study start: 6 Jun 2019 (actual)
Primary completion: 9 Aug 2019 (actual)
Study completion: 9 Aug 2019 (actual)
First posted: 23 May 2019 (actual)
Results: Posted 7 Sep 2020

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Part 1	Experimental	Drug: Entrectinib 600 mg (T1), Drug: Entrectinib 600 mg (T2), Drug: Entrectinib 200 mg (R)Participants will be randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants will cross-over to three periods taking different formulations of entrectinib. Entrectinib will be administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule.
Part 2	Experimental	Drug: Entrectinib 200 mg (R), Drug: Entrectinib 200 mg (T)Participants will be randomly assigned to one of the two treatment sequences (TR, RT). In each treatment sequences, participants will cross-over to two periods taking different formulations of entrectinib. Entrectinib will be administered as a single 200 mg oral dose under fasted condition in two different formulations. Test formulation (T): hydroxypropyl methylcellulose (HPMC) capsule; Reference formulation (R): hard capsule.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (2 listed)

A body mass index (BMI) between 18.0 and 32.0 kilogram per square meter (kg/m2), inclusive, and weighing >/=50 kg.
Agreement to comply with measures to prevent pregnancy and restrictions on egg and sperm donation

Key exclusion criteria (9 listed)

Women of childbearing potential, women who are pregnant or breastfeeding, or intending to become pregnant during the study or within 14 days after the final dose of entrectinib or have a pregnant partner
A clinical significant medical history of gastrointestinal surgery (e.g., gastric bypass) or other gastrointestinal disorder (e.g., malabsorption syndrome) that might affect absorption of medicines from the gastrointestinal tract
Presence of a clinically significant disease, illness, medical condition or disorder, or any other medical history determined by the investigator to be clinically significant and relevant
Clinically significant change in health status, or any major illness, or clinically significant acute infection or febrile illness
Use of moderate or potent inhibitors or inducers of CYP P450 3A4 enzyme or P-gp transporter, or use of other prohibited medications

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
Entrectinib 600 mg (T1)Test formulation 1 (T1): Multi-particulate formulation 1: entrectinib film-coated mini-tablets	Drug	Part 1
Entrectinib 600 mg (T2)Test formulation 2 (T2): Multi-particulate formulation 2: entrectinib film-coated mini-tablets	Drug	Part 1
Entrectinib 200 mg (R)Reference formulation (R): entrectinib hard capsules	Drug	Part 1, Part 2
Entrectinib 200 mg (T)Test formulation (T): entrectinib HPMC capsules	Drug	Part 2

Primary outcome

Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Entrectinib
Time frame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
AUC0-inf of Entrectinib Active Metabolite M5
Time frame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
Maximum Plasma Concentration (Cmax) of Entrectinib
Time frame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
Cmax of Entrectinib Active Metabolite M5
Time frame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)

1 secondary outcome

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From Day -1 to Day 5 of each periods (each period=7 days)

Results and safety

Results posted to the registry on 7 Sep 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1 T1T2R Sequence	5	5
Part 1 T2RT1 Sequence	5	5
Part 1 RT1T2 Sequence	5	5
Part 2 TR Sequence	0	0
Part 2 RT Sequence	0	0

Primary outcome: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Entrectinib

Time frame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days). Geometric mean (Geometric Coefficient of Variation). Unit: nmol*h/L

Measure	Part 1 T1/F15 (Test Formulation 1) n = 15	Part 1 T2/F16 (Test Formulation 2) n = 15	Part 1 R/F06 (Reference Formulation) n = 15	Part 2 T/F06 Coarse (Test Formulation) n = 16	Part 2 R/F06 Fine (Reference Formulation) n = 16
Value	41500 (38.2)	46600 (34.5)	43400 (40.9)	9860 (64.7)	10100 (56.0)

Population analysed: The analysis population included all participants in Part 1 and Part 2, who received at least one dose of entrectinib. Only participants for whom data were collected are included in the analysis.

Primary outcome: AUC0-inf of Entrectinib Active Metabolite M5

Time frame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days). Geometric mean (Geometric Coefficient of Variation). Unit: nmol*h/L

Measure	Part 1 T1/F15 (Test Formulation 1) n = 15	Part 1 T2/F16 (Test Formulation 2) n = 15	Part 1 R/F06 (Reference Formulation) n = 15	Part 2 T/F06 Coarse (Test Formulation) n = 16	Part 2 R/F06 Fine (Reference Formulation) n = 16
Value	12400 (31.1)	12200 (20.9)	13600 (31.7)	3900 (42.8)	3780 (28.1)

Primary outcome: Maximum Plasma Concentration (Cmax) of Entrectinib

Time frame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days). Geometric mean (Geometric Coefficient of Variation). Unit: nmol/L

Measure	Part 1 T1/F15 (Test Formulation 1) n = 15	Part 1 T2/F16 (Test Formulation 2) n = 15	Part 1 R/F06 (Reference Formulation) n = 15	Part 2 T/F06 Coarse (Test Formulation) n = 16	Part 2 R/F06 Fine (Reference Formulation) n = 16
Value	1930 (24.9)	1940 (21.3)	1880 (26.1)	494 (54.7)	522 (33.8)

Primary outcome: Cmax of Entrectinib Active Metabolite M5

Time frame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days). Geometric mean (Geometric Coefficient of Variation). Unit: nmol/L

Measure	Part 1 T1/F15 (Test Formulation 1) n = 15	Part 1 T2/F16 (Test Formulation 2) n = 15	Part 1 R/F06 (Reference Formulation) n = 15	Part 2 T/F06 Coarse (Test Formulation) n = 16	Part 2 R/F06 Fine (Reference Formulation) n = 16
Value	398 (32.2)	325 (32.3)	360 (30.1)	100 (63.2)	113 (42.4)

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Day -1 through Day 5 of each period in both Part 1 and Part 2 (one period=7 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1 T1/F15 (Test Formulation 1)	0 of 15 (0%)	15 of 15 (100%)	0 of 15
Part 1 T2/F16 (Test Formulation 2)	0 of 15 (0%)	14 of 15 (93.3%)	0 of 15
Part 1 R/F06 (Reference Formulation)	0 of 15 (0%)	15 of 15 (100%)	0 of 15
Part 2 T/F06 Coarse (Test Formulation)	0 of 16 (0%)	5 of 16 (31.3%)	0 of 16
Part 2 R/F06 Fine (Reference Formulation)	0 of 16 (0%)	6 of 16 (37.5%)	0 of 16

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No. Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Related trials for 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
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

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

1 site 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 600 mg (T1), Entrectinib 600 mg (T2) and Entrectinib 200 mg (R) in people with Solid Tumor, run by Genentech, Inc. at 1 site in United Kingdom.

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 2 inclusion and 9 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 7 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. 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?

Yes. Results are posted in the registry (first posted 7 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Entrectinib (time frame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)). The study lists 4 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 NCT03961100.

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 7 Sep 2020.