A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate, Midazolam, in Participants With ALK-Positive or ROS1-Positive Solid Tumors

NCT ID: NCT03420742

Last Updated: 2023-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-26
• Study Completion Date: 2021-04-29

Brief Summary

The purpose of this study is to characterize the effect of repeat-dose administration of brigatinib 180 milligram (mg) once daily (QD) on the single-dose pharmacokinetics (PK) of midazolam.

Detailed Description

The study will enroll approximately 20 participants to achieve approximately 15 PK-evaluable participants for assessment. This study will consist of 2 parts: Part A of the study will evaluate the effect of repeat-dose administration of brigatinib on the single-dose PK of midazolam. Part B of the study is exploratory and will allow participants to continue brigatinib until disease progression (PD). All participants will receive study drug via the oral route. Participants will be assigned to: Midazolam 3 mg + Brigatinib 90 mg.

The overall time to participate in this study is 26 months. Participants will have a 28-day PK cycle in Part A and a maximum of 23 cycles in Part B, and a 30-day follow-up period after end of treatment.

Conditions

Carcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Midazolam 3 mg + Brigatinib 90 mg

Midazolam 3 mg, orally, once on Day 1, followed by brigatinib 90 mg, orally, once daily on Days 2 to 8, further followed by brigatinib 180 mg, orally, once daily on Days 9 to 28 in Part A Cycle 1 (28 days treatment cycle). Participants escalating to brigatinib 180 mg once daily will also receive midazolam 3 mg, orally, once on Day 21 of Part A Cycle 1. After completion of Part A, participants will continue into Part B. Participants in Part B will receive brigatinib up to 180 mg (or at the highest tolerated dose in Part A), orally, once daily in a 28 day treatment cycle, up to a maximum of 23 cycles or until progression of disease, unacceptable toxicity, or another discontinuation criterion is met.

Group Type: EXPERIMENTAL

Midazolam

Intervention Type: DRUG

Midazolam syrup.

Brigatinib

Intervention Type: DRUG

Brigatinib tablets.

Interventions

Midazolam

Midazolam syrup.

Intervention Type: DRUG

Brigatinib

Brigatinib tablets.

Intervention Type: DRUG

Other Intervention Names

Alunbrig

Eligibility Criteria

Inclusion Criteria

1. Locally advanced or metastatic solid tumors who meet 1 of the following 4 criteria:

• With locally advanced or metastatic ALK-positive NSCLC who have progressed on or are intolerant to treatment with at least 1 other ALK inhibitor.
• With ALK-positive nonlung solid tumors that are locally advanced or metastatic and for whom no standard, nonexperimental therapy is available.
• With locally advanced or metastatic ROS1-positive NSCLC who have progressed on crizotinib therapy or are intolerant to crizotinib, or
• With ROS1-positive nonlung solid tumors that are locally advanced or metastatic and for whom no standard, nonexperimental therapy is available.

2. Eastern cooperative Oncology Group (ECOG) performance status of 0 or 1.

3. Have at least 1 target lesion per response evaluation criteria in solid tumors (RECIST) version 1.1.

4. Have recovered from toxicities related to prior anticancer therapy to National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 4.03 Grade less than or equal to (<=) 1.

5. Suitable venous access for study-required blood sampling (that is, including PK and laboratory safety tests).

Exclusion Criteria

1. Systemic treatment with strong or moderate cytochrome P450 3A (CYP3A) inhibitors or inducers within 14 days before enrollment.

2. Prior therapy with brigatinib.

3. Received prior ALK-inhibitor therapy within 7 days before the first dose of study drug.

4. Treatment with any investigational systemic anticancer agents within 14 days or 5 half-lives, whichever is longer, before the first dose of study drug.

5. Received chemotherapy or radiation therapy within 14 days before the first dose of study drug, except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.

6. Received antineoplastic monoclonal antibodies within 30 days before the first dose of study drug.

7. Had major surgery within 30 days before the first dose of study drug. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.

8. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Hopital de la Timone

Marseille, Provence-Alpes-Côte d'Azur Region, France

Groupe Hospitalier Bichat-Claude Bernard - Hopital Bichat

Paris, Île-de-France Region, France

Centro di Riferimento Oncologico di Aviano

Aviano, Pordenone, Italy

Policlinico Sant'Orsola Malpighi

Bologna, , Italy

Ospedale San Raffaele

Milan, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Azienda Ospedaliero Universitaria di Parma

Parma, , Italy

Ospedale Santa Maria delle Croci

Ravenna, , Italy

Netherlands Cancer Institute

Amsterdam, North Holland, Netherlands

Hospital Universitario Dexeus

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario Ramon Y Cajal

Madrid, , Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

HM Centro Integral Oncologico Clara Campal

Madrid, , Spain

Countries

France; Italy; Netherlands; Spain

References

Hanley MJ, D'Arcangelo M, Felip E, Garrido P, Zhu J, Ye M, Vranceanu F, Gupta N. A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate Midazolam in Patients With ALK-Positive or ROS1-Positive Solid Tumors. J Clin Pharmacol. 2023 May;63(5):583-592. doi: 10.1002/jcph.2198. Epub 2023 Jan 27.

Reference Type: DERIVED

PMID: 36579743 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1203-0166

Identifier Type: OTHER

Identifier Source: secondary_id

2018-001624-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Brigatinib-1001

Identifier Type: -

Identifier Source: org_study_id