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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01772797
First received: January 17, 2013
Last updated: April 25, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Anaplastic Lymphoma Kinase (ALK)
Non-small Cell Lung Cancer
Drug: LDK378
Drug: AUY922
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-label, Dose Escalation Study of LDK378 and AUY922 in Patients With ALK-rearranged Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence rate of Dose Limiting Toxicities (DLT) [ Time Frame: up to day 28 after the patient's first dose ] [ Designated as safety issue: Yes ]
    cycle = within the first 28 days of patient's first dose


Secondary Outcome Measures:
  • Number of patients with adverse events [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LDK378 and AUY922 in patients

  • Changes in laboratory values [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LDK378 and AUY922 in patients

  • Assessments of electrocardiograms [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LDK378 and AUY922 in patients

  • Assessments of dose interruptions, reductions, and dose intensity [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LDK378 and AUY922 in patients

  • Plasma PK parameter of LDK378 and AUY922: Tmax [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple dose PK of LDK378 and AUY922 in patients

  • Overall response rate (ORR) [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LDK378 and AUY922

  • Duration of Response (DoR) [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LDK378 and AUY922

  • Time to Response (TTR) [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LDK378 and AUY922

  • Progression free survival (PFS) [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LDK378 and AUY922 per RECIST 1.1

  • Number of patients with serious adverse events [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LDK378 and AUY922 in patients

  • Plasma PK parameter of LDK378 and AUY922: Cmax [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple dose PK of LDK378 and AUY922 in patients

  • Plasma PK parameter of LDK378 and AUY922: AUClast [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple dose PK of LDK378 and AUY922 in patients

  • Plasma PK parameter of LDK378 and AUY922: AUCtau [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple dose PK of LDK378 and AUY922 in patients

  • Plasma PK parameter of LDK378 and AUY922: Cmin [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple dose PK of LDK378 and AUY922 in patients

  • Plasma PK parameter of LDK378 and AUY922: Racc [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple dose PK of LDK378 and AUY922 in patients


Enrollment: 22
Study Start Date: June 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772797

Locations
United States, Colorado
University of Colorado Dept. of Anschutz Cancer (3)
Aurora, Colorado, United States, 80045
United States, Massachusetts
Massachusetts General Hospital Mass General
Boston, Massachusetts, United States, 02114
United States, Pennsylvania
Fox Chase Cancer Center Fox Chase Cancer (2)
Philadelphia, Pennsylvania, United States, 19111-2497
United States, Utah
University of Utah / Huntsman Cancer Institute Huntsman
Salt Lake City, Utah, United States, 84103
Australia, Victoria
Novartis Investigative Site
East Melbourne, Victoria, Australia, 3002
Italy
Novartis Investigative Site
Milano, MI, Italy, 20141
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01772797     History of Changes
Other Study ID Numbers: CLDK378X2102, 2012-004632-29
Study First Received: January 17, 2013
Last Updated: April 25, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
anaplastic lymphoma kinase, ALK-rearranged lung cancer, non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Ceritinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on May 26, 2015