Carcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors Clinical Trial
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
| Verified date | April 2022 |
| Source | Takeda |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 24 |
| Est. completion date | April 29, 2021 |
| Est. primary completion date | March 24, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| France | Hopital de la Timone | Marseille | Provence Alpes COTE D'azur |
| France | Groupe Hospitalier Bichat-Claude Bernard - Hopital Bichat | Paris | Ile-de-france |
| Italy | Centro di Riferimento Oncologico di Aviano | Aviano | Pordenone |
| Italy | Policlinico Sant'Orsola Malpighi | Bologna | |
| Italy | Istituto Europeo di Oncologia | Milano | |
| Italy | Ospedale San Raffaele | Milano | |
| Italy | Azienda Ospedaliero Universitaria di Parma | Parma | |
| Italy | Ospedale Santa Maria delle Croci | Ravenna | |
| Netherlands | Netherlands Cancer Institute | Amsterdam | Noord-holland |
| Spain | Hospital Universitari Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitario Dexeus | Barcelona | |
| Spain | HM Centro Integral Oncologico Clara Campal | Madrid | |
| Spain | Hospital Universitario Fundacion Jimenez Diaz | Madrid | |
| Spain | Hospital Universitario Ramon Y Cajal | Madrid |
| Lead Sponsor | Collaborator |
|---|---|
| Takeda |
France, Italy, Netherlands, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Part A, AUC8: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam | The statistical analysis was calculated via a mixed-effects analysis of variance (ANOVA) fitting terms for treatment (midazolam with or without brigatinib coadministration). | 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) | |
| Primary | Part A, Cmax: Maximum Observed Plasma Concentration for Midazolam | The statistical analysis was calculated via a mixed-effects ANOVA fitting terms for treatment (midazolam with or without brigatinib coadministration). | 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) | |
| Primary | Part A, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Midazolam | 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) |