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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03420742
Recruitment Status : Active, not recruiting
First Posted : February 5, 2018
Last Update Posted : May 13, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda ( Ariad Pharmaceuticals )

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
Carcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors Drug: Midazolam Drug: Brigatinib 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
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 : June 26, 2019
Actual Primary Completion Date : March 25, 2020
Estimated Study Completion Date : May 18, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

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 Name: Alunbrig




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


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03420742


Locations
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France
Groupe Hospitalier Bichat-Claude Bernard - Hopital Bichat
Paris, Ile-de-france, France, 75018
Hopital de la Timone
Marseille, Provence Alpes COTE D'azur, France, 13005
Italy
Centro di Riferimento Oncologico di Aviano
Aviano, Pordenone, Italy, 33081
Policlinico Sant'Orsola Malpighi
Bologna, Italy, 40138
Ospedale San Raffaele
Milano, Italy, 20132
Istituto Europeo di Oncologia
Milano, Italy, 20141
Azienda Ospedaliero Universitaria di Parma
Parma, Italy, 43126
Ospedale Santa Maria delle Croci
Ravenna, Italy, 48121
Netherlands
Netherlands Cancer Institute
Amsterdam, Noord-holland, Netherlands, 1066 CX
Spain
Hospital Universitario Dexeus
Barcelona, Spain, 8028
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 8035
Hospital Universitario Ramon Y Cajal
Madrid, Spain, 28034
Hospital Universitario Fundacion Jimenez Diaz
Madrid, Spain, 28040
HM Centro Integral Oncologico Clara Campal
Madrid, Spain, 28050
Sponsors and Collaborators
Ariad Pharmaceuticals
Investigators
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Study Director: Medical Director Ariad Pharmaceuticals
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Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03420742    
Other Study ID Numbers: Brigatinib-1001
U1111-1203-0166 ( Other Identifier: WHO )
2018-001624-19 ( EudraCT Number )
First Posted: February 5, 2018    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Ariad Pharmaceuticals ):
Drug therapy, brigatinib, lung cancer, ALK, ROS1
Additional relevant MeSH terms:
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Neoplasms
Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action