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

Sponsor
Ariad Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03420742
Collaborator
(none)
24
Enrollment
14
Locations
1
Arm
22.1
Actual Duration (Months)
1.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate Midazolam in Patients With ALK-Positive or ROS1-Positive Solid Tumors
Actual Study Start Date :
Jun 26, 2019
Actual Primary Completion Date :
Mar 25, 2020
Actual Study Completion Date :
Apr 29, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Midazolam
Midazolam syrup.

Drug: Brigatinib
Brigatinib tablets.
Other Names:
  • Alunbrig

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Part A: AUC∞: Area Under the Plasma Concentration-Time Curve from Time 0 to Infinity (AUC∞) for Midazolam [Days 1 and 21 pre-dose and at multiple time points (up to 24 hours) post-dose]

    2. Part A: Cmax: Maximum Observed Plasma Concentration for Midazolam [Days 1 and 21 pre-dose and at multiple time points (up to 24 hours) post-dose]

    3. Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Midazolam [Days 1 and 21 pre-dose and at multiple time points (up to 24 hours) post-dose]

    Eligibility Criteria

    Criteria

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

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

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

    3. 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.

    4. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Groupe Hospitalier Bichat-Claude Bernard - Hopital Bichat Paris Ile-de-france France 75018
    2 Hopital de la Timone Marseille Provence Alpes COTE D'azur France 13005
    3 Centro di Riferimento Oncologico di Aviano Aviano Pordenone Italy 33081
    4 Policlinico Sant'Orsola Malpighi Bologna Italy 40138
    5 Ospedale San Raffaele Milano Italy 20132
    6 Istituto Europeo di Oncologia Milano Italy 20141
    7 Azienda Ospedaliero Universitaria di Parma Parma Italy 43126
    8 Ospedale Santa Maria delle Croci Ravenna Italy 48121
    9 Netherlands Cancer Institute Amsterdam Noord-holland Netherlands 1066 CX
    10 Hospital Universitario Dexeus Barcelona Spain 8028
    11 Hospital Universitari Vall d'Hebron Barcelona Spain 8035
    12 Hospital Universitario Ramon Y Cajal Madrid Spain 28034
    13 Hospital Universitario Fundacion Jimenez Diaz Madrid Spain 28040
    14 HM Centro Integral Oncologico Clara Campal Madrid Spain 28050

    Sponsors and Collaborators

    • Ariad Pharmaceuticals

    Investigators

    • Study Director: Medical Director, Ariad Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ariad Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03420742
    Other Study ID Numbers:
    • Brigatinib-1001
    • U1111-1203-0166
    • 2018-001624-19
    First Posted:
    Feb 5, 2018
    Last Update Posted:
    May 21, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Ariad Pharmaceuticals
    Drug therapy, brigatinib, lung cancer, ALK, ROS1
    Additional relevant MeSH terms:
    Neoplasms
    Midazolam

    Study Results

    No Results Posted as of May 21, 2021