Clinical trial NCT03420742: A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate, Midazolam, in Participants With ALK-Positive or ROS1-Positive Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors
Keywords: Drug therapy, brigatinib, lung cancer, ALK, ROS1
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-02-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Part A, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam
timeFrame: Cycle 1, Days 1 (Midazolam alone) and 21 (Midazolam + Brigatinib): pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length is 28 days)
measure: Part A, Cmax: Maximum Observed Plasma Concentration for Midazolam
timeFrame: Cycle 1, Days 1 (Midazolam alone) and 21 (Midazolam + Brigatinib): pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length is 28 days)
measure: Part A, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Midazolam
timeFrame: Cycle 1, Days 1 (Midazolam alone) and 21 (Midazolam + Brigatinib): pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length is 28 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Bichat-Claude Bernard - Hopital Bichat
state: Ile-de-france
city: Marseille
country: France
facility: Hopital de la Timone
state: Provence Alpes COTE D'azur
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico di Aviano
state: Pordenone
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
state: Noord-holland
city: Barcelona
country: Spain
facility: Hospital Universitario Dexeus
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: HM Centro Integral Oncologico Clara Campal
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: