A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam in Patients With ALK-positive Advanced Tumors
The purpose of this study was to evaluate the potential inhibitory effects of ceritinib on the CYP3A4- and CYP2C9-mediated metabolism of the probe drugs midazolam and warfarin, respectively, when administered simultaneously as a cocktail. The results obtained from this drug interaction study would provide guidance that would enable an update to the ceritinib labeling and ouldl help guide recommendations for administration of co-medications in future clinical trials.
Ask AI to explain this studyKey things to know
This describes the study’s primary purpose.
Plus 1 other study approaches.
These are broad labels—not an eligibility decision.
Checked against the public recordLast updated Dec 19, 2020 · Source: ClinicalTrials.gov
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Interventional
Locations may change over time.
Study sponsor
What this study is about
- Purpose
- Other
- Study type
- Interventional
- Phase
- Phase 1
- Sponsor
- Novartis Pharmaceuticals
- Interventions being studied
- Drug: ceritinib; Drug: warfarin; Drug: midazolam
How this study is categorized
These labels come from structured fields and exact terms in the public record.
Who may be able to participate
The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.
- Histologically or cytologically confirmed diagnosis of stage IIIB (and is not a candidate for definitive multimodality therapy) or stage IV NSCLC demonstrated ALK-positive or an advanced tumor, other than NSCLC, that carries an ALK genetic alteration (mutation, translocation or amplification) and/or ALK overexpression that has progressed despite standard therapy, or for which no effective standard therapy exists.
- The test to confirm ALK-positivity may be performed in archival tumor (obtained at or since the time of diagnosis), or in a newly obtained tumor sample taken prior to the first day of study drug. Results confirming ALK-positive status must be available before initiating treatment with ceritinib.
- Patients who have received prior chemotherapy, other ALK inhibitors, biologic therapy, or other investigational agents, must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03) prior to starting study drug. Patients with grade ≤ 2 peripheral neuropathy or any grade of alopecia, nail changes or skin changes are allowed to enter the study.
- Patients who have been treated with chemotherapy, with biological therapy or other investigational agent must have discontinued the treatment at least 2 weeks (14 days) prior to starting the study drug on Study Day 1.In case last chemotherapy contained nitrosourea or mitomycin C, the treatment was discontinued at least 6 weeks prior to starting study drug.
- Patient has the ability to understand and provide signed informed consent.
- Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate), midazolam and warfarin as described in the local product information.
- History of carcinomatous meningitis.
- Presence or history of a malignant disease other than an ALK-positive advanced tumor that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:
- Unstable angina within 6 months prior to screening.
- Myocardial infarction within 6 months prior to screening.
- History of documented congestive heart failure (New York Heart Association functional classification III-IV).
- Uncontrolled hypertension defined by a Systolic Blood Pressure ≥ 160 mmHg and/or Diastolic Blood Pressure ≥ 100 mmHg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication (s) was allowed prior to screening.
- Ventricular arrhythmias.
- Supraventricular and nodal arrhythmias not controlled with medication.
- Other cardiac arrhythmia not controlled with medication.
- Corrected QT (QTcF) \> 470 ms using Fridericia's correction on the screening electrocardiogram (ECG) (as mean of triplicate ECGs).
- Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100 mmHg, with or without anti-hypertensive medication.
- Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention). Other Protocol defined Inclusion/Exclusion may applied.
Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.
U.S. locations
- Karmanos Cancer Institute Oncology DepartmentDetroit, Michigan
- Henry Ford Hospital SCDetroit, Michigan
- Cancer Therapy & Research Center UT Health Science Center SC-4San Antonio, Texas
- Novartis Investigative SiteCopenhagen
- Novartis Investigative SiteMilan, MI
- Novartis Investigative SiteRozzano, MI
- Novartis Investigative SiteModena, MO
- Novartis Investigative SitePadova, PD
- Novartis Investigative SiteA Coruña, Galicia
- Novartis Investigative SiteMadrid
- Novartis Investigative SiteMadrid
Source and freshness
Processed from ClinicalTrials.gov. Last public update: Dec 19, 2020. Always confirm current availability with the study team.