Anaplastic Lymphoma Kinase (ALK)Phase 1NCT01772797
Phase Ib Study of LDK378 and AUY922 in ALK-rearranged Non-small Cell Lung Cancer
A Phase 1 study testing LDK378 and AUY922 in people with Anaplastic Lymphoma Kinase (ALK) and Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 8 sites in 5 countries.
Trial summary
The primary purpose of the study is to estimate the maximum tolerated dose of the combination of LDK378 and AUY922. This study will assess the safety, tolerability, pharmacokinetics and preliminary evidence of anti-tumor activity of the combination of LDK378 and AUY922 in ALK-rearranged non-small cell lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anaplastic Lymphoma Kinase (ALK), Non-small Cell Lung Cancer
- What is being tested?
- LDK378 and AUY922
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 8 sitesin 5 countries
- Study dates
- Jun 2013to Jan 2016
- 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
- locally advanced or metastatic NSCLC that has progressed during or following therapy with an ALK inhibitor
- tumor must carry an ALK rearrangement in 15% or more of tumor cells as measured by FISH
- disease that can be evaluated by RECIST v1.1 and measurable disease
Who cannot join
- central nervous system (CNS) metastases that are symptomatic or require increasing steroids or CNS-directed therapy to control CNS disease
- history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis
- clinically significant cardiac dysfunction
- inadequate end organ function as defined by specified laboratory values
- use of medications known to be strong inhibitors or inducters of CYP3A4/5 that cannot be discontinued at least 1 week prior to start of treatment
- use of medications that are mainly metabolized by CYP3A4/5 or CYP2C9 that cannot be discontinued at least 1 week prior to start of treatment
Show all 11Show fewer
- clinically significant, uncontrolled impaired gastrointestinal function or GI disease
- prior treatment with a HSP90 inhibitor
- radiotherapy to lung within 4 weeks prior to the first dose of study treatment or patients who have not recovered from radiotherapy-related toxicities
- pregnant or nursing women
- history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
United States4 sites
University of Colorado Dept. of Anschutz Cancer (3)
Aurora, Colorado, 80045
Massachusetts General Hospital Mass General
Boston, Massachusetts, 02114
Fox Chase Cancer Center Fox Chase Cancer (2)
Philadelphia, Pennsylvania, 19111-2497
University of Utah / Huntsman Cancer Institute Huntsman
Salt Lake City, Utah, 84103
About this study
Official title: A Phase Ib, Open-label, Dose Escalation Study of LDK378 and AUY922 in Patients With ALK-rearranged Non-small Cell Lung Cancer
The primary purpose of the study is to estimate the maximum tolerated dose of the combination of LDK378 and AUY922. This study will assess the safety, tolerability, pharmacokinetics and preliminary evidence of anti-tumor activity of the combination of LDK378 and AUY922 in ALK-rearranged non-small cell lung cancer.
- Being tested
- LDK378, AUY922
- Keywords
- anaplastic lymphoma kinase, ALK-rearranged lung cancer, non-small cell lung cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDK378Drug
LDK378 is a capsule to be taken daily by mouth.
AUY922Drug
AUY922 is an intravenous infusion that will be administered by the investigative site to the patient on a weekly basis.
| Study group | Role | What they receive |
|---|---|---|
| LDK378 and AUY922 | Experimental | Not described Receives: Drug: LDK378; Drug: AUY922 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rate of Dose Limiting Toxicities (DLT)
cycle = within the first 28 days of patient's first dose
Measured: up to day 28 after the patient's first dose
Secondary outcomes (15)
Number of patients with adverse events
Characterize the safety and tolerability of LDK378 and AUY922 in patients
Measured: 30 months
Changes in laboratory values
Characterize the safety and tolerability of LDK378 and AUY922 in patients
Measured: 30 months
Assessments of electrocardiograms
Characterize the safety and tolerability of LDK378 and AUY922 in patients
Measured: 30 months
Assessments of dose interruptions, reductions, and dose intensity
Characterize the safety and tolerability of LDK378 and AUY922 in patients
Measured: 30 months
Plasma PK parameter of LDK378 and AUY922: Tmax
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Measured: 30 months
Overall response rate (ORR)
Assess the anti-tumor activity of LDK378 and AUY922
Measured: 30 months
Duration of Response (DoR)
Assess the anti-tumor activity of LDK378 and AUY922
Measured: 30 months
Time to Response (TTR)
Assess the anti-tumor activity of LDK378 and AUY922
Measured: 30 months
Progression free survival (PFS)
Assess the anti-tumor activity of LDK378 and AUY922 per RECIST 1.1
Measured: 30 months
Number of patients with serious adverse events
Characterize the safety and tolerability of LDK378 and AUY922 in patients
Measured: 30 months
Plasma PK parameter of LDK378 and AUY922: Cmax
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Measured: 30 months
Plasma PK parameter of LDK378 and AUY922: AUClast
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Measured: 30 months
Plasma PK parameter of LDK378 and AUY922: AUCtau
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Measured: 30 months
Plasma PK parameter of LDK378 and AUY922: Cmin
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Measured: 30 months
Plasma PK parameter of LDK378 and AUY922: Racc
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2013 (estimated)
- Study startJun 2013
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anaplastic Lymphoma Kinase (ALK)Studies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 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
- NCT01772797
- Sponsor's protocol ID
- CLDK378X2102
- Other IDs
- 2012-004632-29
- Status last verified
- Sep 2016
- First submitted
- 17 Jan 2013
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- 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 Ib, Open-label, Dose Escalation Study of LDK378 and AUY922 in Patients With ALK-rearranged Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01772797
- Acronym / sponsor ID
- CLDK378X2102
- Keywords
- anaplastic lymphoma kinase, ALK-rearranged lung cancer, non-small cell lung cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 21 Jan 2013 (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 primary purpose of the study is to estimate the maximum tolerated dose of the combination of LDK378 and AUY922. This study will assess the safety, tolerability, pharmacokinetics and preliminary evidence of anti-tumor activity of the combination of LDK378 and AUY922 in ALK-rearranged non-small cell lung cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LDK378 and AUY922 | Experimental | Drug: LDK378, Drug: AUY922 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- locally advanced or metastatic NSCLC that has progressed during or following therapy with an ALK inhibitor
- tumor must carry an ALK rearrangement in 15% or more of tumor cells as measured by FISH
- disease that can be evaluated by RECIST v1.1 and measurable disease
Key exclusion criteria (11 listed)
- central nervous system (CNS) metastases that are symptomatic or require increasing steroids or CNS-directed therapy to control CNS disease
- history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis
- clinically significant cardiac dysfunction
- inadequate end organ function as defined by specified laboratory values
- use of medications known to be strong inhibitors or inducters of CYP3A4/5 that cannot be discontinued at least 1 week prior to start of treatment
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 |
|---|---|---|
| LDK378LDK378 is a capsule to be taken daily by mouth. | Drug | LDK378 and AUY922 |
| AUY922AUY922 is an intravenous infusion that will be administered by the investigative site to the patient on a weekly basis. | Drug | LDK378 and AUY922 |
Primary outcome
Incidence rate of Dose Limiting Toxicities (DLT)
Time frame: up to day 28 after the patient's first dose
cycle = within the first 28 days of patient's first dose
15 secondary outcomes
Number of patients with adverse events
Time frame: 30 months
Changes in laboratory values
Time frame: 30 months
Assessments of electrocardiograms
Time frame: 30 months
Assessments of dose interruptions, reductions, and dose intensity
Time frame: 30 months
Plasma PK parameter of LDK378 and AUY922: Tmax
Time frame: 30 months
Overall response rate (ORR)
Time frame: 30 months
Duration of Response (DoR)
Time frame: 30 months
Time to Response (TTR)
Time frame: 30 months
Progression free survival (PFS)
Time frame: 30 months
Number of patients with serious adverse events
Time frame: 30 months
Plasma PK parameter of LDK378 and AUY922: Cmax
Time frame: 30 months
Plasma PK parameter of LDK378 and AUY922: AUClast
Time frame: 30 months
Plasma PK parameter of LDK378 and AUY922: AUCtau
Time frame: 30 months
Plasma PK parameter of LDK378 and AUY922: Cmin
Time frame: 30 months
Plasma PK parameter of LDK378 and AUY922: Racc
Time frame: 30 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 19 Dec 2020.
- Results for CLDK378X2102 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
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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 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LDK378 and AUY922 in people with Anaplastic Lymphoma Kinase (ALK) and Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 8 sites in 5 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 3 inclusion and 11 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 8 sites in United States, Australia, Italy, Singapore, Spain. 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 (DLT) (time frame: up to day 28 after the patient's first dose). 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.