Phase Ib Study of LDK378 and AUY922 in ALK-rearranged Non-small Cell Lung Cancer

December 16, 2020 updated by: Novartis Pharmaceuticals

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
22

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Novartis Investigative Site
  • Italy
    • MI
      • Milano, MI, Italy, 20141
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 169610
        • Novartis Investigative Site
  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Dept. of Anschutz Cancer (3)
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Mass General
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center Fox Chase Cancer (2)
    • Utah
      • Salt Lake City, Utah, United States, 84103
        • University of Utah / Huntsman Cancer Institute Huntsman

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: LDK378 and AUY922
Drug: LDK378
LDK378 is a capsule to be taken daily by mouth.
Drug: AUY922
AUY922 is an intravenous infusion that will be administered by the investigative site to the patient on a weekly basis.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
up to day 28 after the patient's first dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of patients with adverse events
Time Frame: 30 months
Characterize the safety and tolerability of LDK378 and AUY922 in patients
30 months
Changes in laboratory values
Time Frame: 30 months
Characterize the safety and tolerability of LDK378 and AUY922 in patients
30 months
Assessments of electrocardiograms
Time Frame: 30 months
Characterize the safety and tolerability of LDK378 and AUY922 in patients
30 months
Assessments of dose interruptions, reductions, and dose intensity
Time Frame: 30 months
Characterize the safety and tolerability of LDK378 and AUY922 in patients
30 months
Plasma PK parameter of LDK378 and AUY922: Tmax
Time Frame: 30 months
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
30 months
Overall response rate (ORR)
Time Frame: 30 months
Assess the anti-tumor activity of LDK378 and AUY922
30 months
Duration of Response (DoR)
Time Frame: 30 months
Assess the anti-tumor activity of LDK378 and AUY922
30 months
Time to Response (TTR)
Time Frame: 30 months
Assess the anti-tumor activity of LDK378 and AUY922
30 months
Progression free survival (PFS)
Time Frame: 30 months
Assess the anti-tumor activity of LDK378 and AUY922 per RECIST 1.1
30 months
Number of patients with serious adverse events
Time Frame: 30 months
Characterize the safety and tolerability of LDK378 and AUY922 in patients
30 months
Plasma PK parameter of LDK378 and AUY922: Cmax
Time Frame: 30 months
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
30 months
Plasma PK parameter of LDK378 and AUY922: AUClast
Time Frame: 30 months
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
30 months
Plasma PK parameter of LDK378 and AUY922: AUCtau
Time Frame: 30 months
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
30 months
Plasma PK parameter of LDK378 and AUY922: Cmin
Time Frame: 30 months
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
30 months
Plasma PK parameter of LDK378 and AUY922: Racc
Time Frame: 30 months
Characterize single and multiple dose PK of LDK378 and AUY922 in patients
30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 17, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 17, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 21, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 19, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLDK378X2102
  • 2012-004632-29 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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