ALK-positive Advanced TumorsPhase 1NCT02422589
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
A Phase 1 study testing ceritinib, warfarin and midazolam in people with ALK-positive Advanced Tumors, run by Novartis Pharmaceuticals at 11 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ALK-positive Advanced Tumors
- What is being tested?
- ceritinib, warfarin and midazolam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 23 Oct 2015to 12 Dec 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
Italy4 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Modena, MO, 41124
Novartis Investigative Site
Padova, PD, 35100
Novartis Investigative Site
Rozzano, MI, 20089
United States3 sites
Karmanos Cancer Institute Oncology Department
Detroit, Michigan, 48201
Henry Ford Hospital SC
Detroit, Michigan, 48202-2689
Cancer Therapy & Research Center UT Health Science Center SC-4
San Antonio, Texas, 78229
Spain3 sites
Novartis Investigative Site
A Coruña, Galicia, 15006
Novartis Investigative Site
Madrid, 28046
Novartis Investigative Site
Madrid, 28050
About this study
Official title: A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam Administered as a Two-drug Cocktail in Patients With ALK-positive Advanced Tumors Including Non-small Cell Lung Cancer (NSCLC)
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.
- Conditions
- ALK-positive Advanced Tumors
- Keywords
- ALK-positive advanced tumors, midazolam, warfarin, ceritinib, ALK, CYP3A-4, Drug drug intereaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Ceritinib | Experimental | Not described Receives: Drug: ceritinib; Drug: warfarin; Drug: midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phamacokinetics (PK) parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not limited to: AUCinf
Measured: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to: AUC
Measured: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 121 days until death or up to 24 months.
PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to:Cmax
Measured: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to:Tmax
Measured: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Secondary outcomes (4)
Ctrough concentrations of ceritinib
Measured: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Number of participants with Adverse Events as a measure of safety and tolerability
This will be done by looking at the vital signs, lab values and ECG
Measured: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Objective Response Rate (ORR)
Tumor evaluation will be determined locally by investigator per RECIST 1.1
Measured: Baseline, every 6 weeks until week 27
Duration of Response (DOR)
Tumor evaluation will be determined locally by investigatorper RECIST 1.1
Measured: Baseline, every 6 weeks until week27
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2015 (estimated)
- Study start23 Oct 2015
- Primary completion12 Dec 2017
- Study completion12 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALK-positive Advanced TumorsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02422589
- Sponsor's protocol ID
- CLDK378A2103
- Other IDs
- 2014-003741-95, 2014
- Status last verified
- Jul 2019
- First submitted
- 16 Mar 2015
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam Administered as a Two-drug Cocktail in Patients With ALK-positive Advanced Tumors Including Non-small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT02422589
- Acronym / sponsor ID
- CLDK378A2103
- Conditions
- ALK-positive Advanced Tumors
- Keywords
- ALK-positive advanced tumors, midazolam, warfarin, ceritinib, ALK, CYP3A-4, Drug drug intereaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 23 Oct 2015 (actual)
- Primary completion
- 12 Dec 2017 (actual)
- Study completion
- 12 Dec 2017 (actual)
- First posted
- 21 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ceritinib | Experimental | Drug: ceritinib, Drug: warfarin, Drug: midazolam |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ceritinib | Drug | Ceritinib |
| warfarin | Drug | Ceritinib |
| midazolam | Drug | Ceritinib |
Primary outcome
Phamacokinetics (PK) parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not limited to: AUCinf
Time frame: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to: AUC
Time frame: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 121 days until death or up to 24 months.
PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to:Cmax
Time frame: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to:Tmax
Time frame: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
4 secondary outcomes
Ctrough concentrations of ceritinib
Time frame: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Number of participants with Adverse Events as a measure of safety and tolerability
Time frame: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Objective Response Rate (ORR)
Time frame: Baseline, every 6 weeks until week 27
Duration of Response (DOR)
Time frame: Baseline, every 6 weeks until week27
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2020.
- Results for CLDK378A2103 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ceritinib, warfarin and midazolam in people with ALK-positive Advanced Tumors, run by Novartis Pharmaceuticals at 11 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Italy, United States, Spain, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phamacokinetics (PK) parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not limited to: AUCinf (time frame: Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2020.