Non-small Cell Lung CancerPhase 1NCT02292550
Study of Safety and Efficacy of LEE011 and Ceritinib in Patients With ALK-positive Non-small Cell Lung Cancer.
A Phase 1 study testing Ribociclib and Ceritinib in people with Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 8 sites in 6 countries.
Trial summary
This was a Phase Ib/II study of the ALK inhibitor ceritinib in combination with the CDK4/6 inhibitor LEE011 in patients with ALK-positive non-small cell lung cancer. The purpose of the study was to determine the MTD/RP2D of the LEE011 and ceritinib combination and evaluate whether the combination was safe and had… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Ribociclib and Ceritinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 8 sitesin 6 countries
- Study dates
- 14 May 2015to 26 Sep 2018
- 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
- Patients must be diagnosed with ALK-positive advanced NSCLC. The tumor must be ALK-positive as determined by ALK rearrangement in ≥15% of cells (as measured by FISH using the Vysis break-apart ALK probe) or by using the Ventana ALK IHC test. The analysis may be performed locally.
- Eastern cooperative oncology group (ECOG) performance status ≤ 2.
- Measurable disease as per RECIST v1.1
- Availability of tumor sample:
- For ALK inhibitor naïve patients:
- o A representative tumor sample must be submitted. An archival tumor specimen is acceptable
- For patients after progression on an ALK inhibitor:
- o A new tumor biopsy is required unless a biopsy performed after progression on the patient's most recent ALK inhibitor is available for submission For all patients a newly obtained tumor specimen must be submitted if no appropriate archival sample is available. In the event that no sample is available and a new biopsy cannot be obtained, enrollment may be considered after discussion with the sponsor.
Who cannot join
- For Phase I part:
- o Patients who have not previously received at least one line of therapy for ALK-positive NSCLC
- For Phase II part:
- Group A: prior therapy with any ALK inhibitor is not permitted.
- Group B: progression following any ALK inhibitor(s) other than ceritinib is required and the last dose of the ALK inhibitor must be no more than 60 days prior to the first dose of study drug. Prior ceritinib is not permitted.
- Group C: progression following ceritinib is required and the last dose of ceritinib must be no more than 60 days prior to the first dose of study drug.
Show all 22Show fewer
- Patients who have previously been unable to tolerate ceritinib, in the opinion of the investigator. Exceptions to this exclusion include nausea, vomiting and diarrhea in patients taking ceritinib under fasted conditions.
- Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy to control their CNS disease
- Patients with abnormal laboratory values during screening and on day 1 of pre-dose
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ceritinib or LEE011
- Patients who are currently receiving treatment (that cannot be discontinued at least 1 week prior to the initiation of the study) with agents that are known to be any of the following: strong inducers or inhibitors of CYP3A4/5; sensitive substrates of CYP3A; substrates of CYP3A4/5 or CYP2C9 with a narrow therapeutic index.
- Patient has a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
- Patient with impaired cardiac function or any clinically significant uncontrolled cardiac disease, and/or, cardiac repolarization abnormality, including any of the following:
- Clinically significant heart disease such as CHF requiring treatment (NYH grade ≥ 2), history of angina pectoris, myocardial infarction, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry, documented cardiomyopathy, or left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO).
- Uncontrolled systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication (s) is allowed prior to screening, Systolic blood pressure (SBP) <90 mmHg Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by central laboratory
- QTcF interval at screening >450 msec (using Fridericia's correction)
- Resting heart rate <50 bpm or > 90 bpm
- Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
- Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
- Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting study drug)
- Inability to determine the QTcF interval Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block).
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
8 sites in 6 countries.
8 sites in 6 countries
Italy2 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Rozzano, MI, 20089
Taiwan2 sites
Novartis Investigative Site
Tainan, Taiwan ROC, 70403
Novartis Investigative Site
Taipei, 10002
United States1 site
Novartis Investigative Site
Boston, Massachusetts, 02114
About this study
Official title: A Phase Ib/II Study of the ALK Inhibitor Ceritinib in Combination With the CDK4/6 Inhibitor LEE011 in Patients With ALK-positive Non-Small Cell Lung Cancer
This was a Phase Ib/II study of the ALK inhibitor ceritinib in combination with the CDK4/6 inhibitor LEE011 in patients with ALK-positive non-small cell lung cancer.
The purpose of the study was to determine the MTD/RP2D of the LEE011 and ceritinib combination and evaluate whether the combination was safe and had beneficial effects in ALK-positive advanced non-small cell lung cancer patients.
This trial did not progress to Phase II. Trial population terminated before reaching Phase II
Read the detailed description
In Sep-2016, Novartis made a decision not to move into phase ll after the primary objective for this study was met. Because the study never made it to phase ll, the study phase has been changed from a phase l/ll to a phase l.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Ribociclib, Ceritinib
- Keywords
- Non-small cell lung cancer, ALK translocation, ALK-positive, NSCLC, LEE011, CDK4/6 inhibitor, EML4-ALK, cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RibociclibDrug
Also called LEE011
CDK 4/6 inhibitor
CeritinibDrug
Also called LDK378, Zykadia
ALK inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Ribociclib 100 mg + Ceritinib 300 mg | Experimental | LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use Receives: Drug: Ribociclib; Drug: Ceritinib |
| Ribociclib 100 mg + Ceritinib 450 mg | Experimental | LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use Receives: Drug: Ribociclib; Drug: Ceritinib |
| Ribociclib 200 mg + Ceritinib 300 mg | Experimental | LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use Receives: Drug: Ribociclib; Drug: Ceritinib |
| Ribociclib 200 mg + Ceritinib 450 mg | Experimental | LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use Receives: Drug: Ribociclib; Drug: Ceritinib |
| Ribociclib 300 mg + Ceritinib 450 mg | Experimental | LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use Receives: Drug: Ribociclib; Drug: Ceritinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment (Phase Ib )
Maximum Tolerated Dose(s) (MTD(s)) and/or recommended phase 2 dose (RP2D(s)) and schedule of LEE011 in combination with ceritinib in ALK-positive non-small cell lung cancer (NSCLC) patients.
Cycle = 28 days
Measured: 1 month
Overall Response Rate (ORR) as per RECIST v1.1
Preliminary anti-tumor activity of the LEE011 and ceritinib combination
Measured: Up to 24 months
Exposure to LEE011 and ceritinib (Phase Ib )
Measurement of pharmacokinetics (PK) parameters (AUC0-24h at C1D15)
Measured: Up to 6 months
Secondary outcomes (10)
Overall Response Rate (ORR) - Phase Ib & II
Preliminary measure of anti-tumor activity of LEE011 and ceritinib combination
Measured: Up to 24 months
Frequency of adverse events/serious adverse events
Characterization of the safety and tolerability of the LEE011 and ceritinib combination as determined by changes in laboratory values and electrocardiograms
Measured: Up to 24 months
PK parameters of LEE011 and ceritinib
Characterization of the PK of LEE011 and ceritinib
Measured: Up to 6 months
Frequency of dose interruptions and dose reductions (phase lb & ll)
Characterization of tolerability
Measured: Up to 24 months
Progression free survival (PFS) per RECIST v1.1 - Phase Ib & II
Preliminary measures of anti-tumor activity of LEE011 and ceritinib combination
Measured: Up to 24 months
Duration of response (DOR)
Preliminary measure of anti-tumor activity of LEE011 and ceritinib combination
Measured: Up to 24 months
Time to response (TTR) - Phase Ib & II
Preliminary measures of anti-tumor activity of LEE011 and ceritinib combination
Measured: Up to 24 months
Disease Control Rate (DCR) - Phase Ib & II
Preliminary measures of anti-tumor activity of LEE011 and ceritinib combination
Measured: Up to 24 months
Overall survival (OS) - Phase Ib & II
Preliminary measures of anti-tumor activity of LEE011 and ceritinib combination
Measured: Up to 24 months
Severity of adverse events/serious adverse events
Characterization of the safety and tolerability of the LEE011 and ceritinib combination as determined by changes in laboratory values and electrocardiograms.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2014 (estimated)
- Study start14 May 2015
- Primary completion26 Sep 2018
- Study completion26 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This was a multi-center, open-label, dose finding, Phase Ib dose escalation study to estimate the maximum tolerated doses (MTD(s))
- Masking
- None (open label)
- Enrolment
- 27 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
- NCT02292550
- Sponsor's protocol ID
- CLEE011X2110C
- Status last verified
- Jul 2019
- First submitted
- 12 Nov 2014
- Last updated
- 17 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of the ALK Inhibitor Ceritinib in Combination With the CDK4/6 Inhibitor LEE011 in Patients With ALK-positive Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02292550
- Acronym / sponsor ID
- CLEE011X2110C
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Non-small cell lung cancer, ALK translocation, ALK-positive, NSCLC, LEE011, CDK4/6 inhibitor, EML4-ALK, cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 14 May 2015 (actual)
- Primary completion
- 26 Sep 2018 (actual)
- Study completion
- 26 Sep 2018 (actual)
- First posted
- 17 Nov 2014 (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.
This was a Phase Ib/II study of the ALK inhibitor ceritinib in combination with the CDK4/6 inhibitor LEE011 in patients with ALK-positive non-small cell lung cancer.
The purpose of the study was to determine the MTD/RP2D of the LEE011 and ceritinib combination and evaluate whether the combination was safe and had beneficial effects in ALK-positive advanced non-small cell lung cancer patients.
This trial did not progress to Phase II. Trial population terminated before reaching Phase II
Detailed description
In Sep-2016, Novartis made a decision not to move into phase ll after the primary objective for this study was met. Because the study never made it to phase ll, the study phase has been changed from a phase l/ll to a phase l.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- This was a multi-center, open-label, dose finding, Phase Ib dose escalation study to estimate the maximum tolerated doses (MTD(s))
| Arm | Type | Receives |
|---|---|---|
| Ribociclib 100 mg + Ceritinib 300 mg | Experimental | Drug: Ribociclib, Drug: CeritinibLEE011 capsule for oral use (ribociclib) and Ceritinib for oral use |
| Ribociclib 100 mg + Ceritinib 450 mg | Experimental | Drug: Ribociclib, Drug: CeritinibLEE011 capsule for oral use (ribociclib) and Ceritinib for oral use |
| Ribociclib 200 mg + Ceritinib 300 mg | Experimental | Drug: Ribociclib, Drug: CeritinibLEE011 capsule for oral use (ribociclib) and Ceritinib for oral use |
| Ribociclib 200 mg + Ceritinib 450 mg | Experimental | Drug: Ribociclib, Drug: CeritinibLEE011 capsule for oral use (ribociclib) and Ceritinib for oral use |
| Ribociclib 300 mg + Ceritinib 450 mg | Experimental | Drug: Ribociclib, Drug: CeritinibLEE011 capsule for oral use (ribociclib) and Ceritinib for oral use |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must be diagnosed with ALK-positive advanced NSCLC. The tumor must be ALK-positive as determined by ALK rearrangement in ≥15% of cells (as measured by FISH using the Vysis break-apart ALK probe) or by using the Ventana ALK IHC test. The analysis may be performed locally.
- Eastern cooperative oncology group (ECOG) performance status ≤ 2.
- Measurable disease as per RECIST v1.1
- Availability of tumor sample:
- o A representative tumor sample must be submitted. An archival tumor specimen is acceptable
Key exclusion criteria (22 listed)
- For Phase I part:
- o Patients who have not previously received at least one line of therapy for ALK-positive NSCLC
- For Phase II part:
- Patients who have previously been unable to tolerate ceritinib, in the opinion of the investigator. Exceptions to this exclusion include nausea, vomiting and diarrhea in patients taking ceritinib under fasted conditions.
- Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy to control their CNS disease
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 |
|---|---|---|
| RibociclibAlso: LEE011CDK 4/6 inhibitor | Drug | Ribociclib 100 mg + Ceritinib 300 mg, Ribociclib 100 mg + Ceritinib 450 mg, Ribociclib 200 mg + Ceritinib 300 mg, Ribociclib 200 mg + Ceritinib 450 mg, Ribociclib 300 mg + Ceritinib 450 mg |
| CeritinibAlso: LDK378, ZykadiaALK inhibitor | Drug | Ribociclib 100 mg + Ceritinib 300 mg, Ribociclib 100 mg + Ceritinib 450 mg, Ribociclib 200 mg + Ceritinib 300 mg, Ribociclib 200 mg + Ceritinib 450 mg, Ribociclib 300 mg + Ceritinib 450 mg |
Primary outcome
Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment (Phase Ib )
Time frame: 1 month
Maximum Tolerated Dose(s) (MTD(s)) and/or recommended phase 2 dose (RP2D(s)) and schedule of LEE011 in combination with ceritinib in ALK-positive non-small cell lung cancer (NSCLC) patients. Cycle = 28 days
Overall Response Rate (ORR) as per RECIST v1.1
Time frame: Up to 24 months
Preliminary anti-tumor activity of the LEE011 and ceritinib combination
Exposure to LEE011 and ceritinib (Phase Ib )
Time frame: Up to 6 months
Measurement of pharmacokinetics (PK) parameters (AUC0-24h at C1D15)
10 secondary outcomes
Overall Response Rate (ORR) - Phase Ib & II
Time frame: Up to 24 months
Frequency of adverse events/serious adverse events
Time frame: Up to 24 months
PK parameters of LEE011 and ceritinib
Time frame: Up to 6 months
Frequency of dose interruptions and dose reductions (phase lb & ll)
Time frame: Up to 24 months
Progression free survival (PFS) per RECIST v1.1 - Phase Ib & II
Time frame: Up to 24 months
Duration of response (DOR)
Time frame: Up to 24 months
Time to response (TTR) - Phase Ib & II
Time frame: Up to 24 months
Disease Control Rate (DCR) - Phase Ib & II
Time frame: Up to 24 months
Overall survival (OS) - Phase Ib & II
Time frame: Up to 24 months
Severity of adverse events/serious adverse events
Time frame: Up to 24 months
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 17 Dec 2020.
- Results for CLEE011X2110C can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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
8 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ribociclib and Ceritinib in people with Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 8 sites in 6 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 8 inclusion and 22 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 17 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 8 sites in Italy, Taiwan, United States, France, South Korea and 1 more country. 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?
Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment (Phase Ib ) (time frame: 1 month). The study lists 3 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 17 Dec 2020.