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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01772797
First received: January 17, 2013
Last updated: March 6, 2014
Last verified: March 2014
  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: 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: 142
Study Start Date: June 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (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

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: Roberta Kay Silveira    +1 720 848 0655    tglass@seattlecca.org   
Principal Investigator: Ross Camidge         
United States, Massachusetts
Massachusetts General Hospital Mass General Recruiting
Boston, Massachusetts, United States, 02115
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: Stephanie Rosati    215-214-4297    Stephanie.Rosati@fccc.edu   
Principal Investigator: Ranee Mehra         
United States, Utah
University of Utah / Huntsman Cancer Institute Huntsman Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Jeff Pettey    801-585-0443    jessica.moehle@hci.utah.edu   
Principal Investigator: Sunil Sharma         
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3002
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20141
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Spain
Novartis Investigative Site Recruiting
Barcelona, Cataluna, 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: March 6, 2014
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 July 10, 2014