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

This study is not yet open for participant recruitment.
Verified January 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01772797
First received: January 17, 2013
Last updated: January 22, 2013
Last verified: January 2013
  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: 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


Estimated Enrollment: 65
Study Start Date: March 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 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
  • 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
  • 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 canno 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01772797

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, Colorado
University of Colorado Dept. of Anschutz Cancer (3) Recruiting
Aurora, Colorado, United States, 80045
Contact: Jessica Bata     720-848-0655     Jessica.bata@ucdenver.edu    
Principal Investigator: Ross Camidge            
United States, Massachusetts
Massachusetts General Hospital Mass General Recruiting
Boston, Massachusetts, United States, 02114
Contact     617-724-1223        
Principal Investigator: Alice Shaw            
United States, Pennsylvania
Fox Chase Cancer Center Fox Chase Cancer (2) Recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Michael Oldfield     215-214-4297     Michael.oldfield@fccc.edu    
Principal Investigator: Ranee Mehra            
United States, Utah
University of Utah / Huntsman Cancer Institute Huntsman Recruiting
Salt Lake City, Utah, United States, 84103
Contact: Jessica Moehle     801-585-0443     jessica.moehle@hci.utah.edu    
Principal Investigator: Sunil Sharma            
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: January 22, 2013
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
Lymphoma
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on May 22, 2013