NCT01283516

Brief Summary

This study assessed the safety and efficacy of LDK378 in adult patients with genetic abnormalities in anaplastic lymphoma kinase (ALK).

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
304

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jan 2011

Longer than P75 for phase_1

Geographic Reach
11 countries

21 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 24, 2011

Completed
Same day until next milestone

Study Start

First participant enrolled

January 24, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 26, 2011

Completed
3.5 years until next milestone

Results Posted

Study results publicly available

August 11, 2014

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 3, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 3, 2016

Completed
Last Updated

March 15, 2019

Status Verified

November 1, 2018

Enrollment Period

5.3 years

First QC Date

January 24, 2011

Results QC Date

May 29, 2014

Last Update Submit

November 28, 2018

Conditions

Tumors Characterized by Genetic Abnormalities of ALK

Keywords

ALK inhibitor,NSCLC,LDK378,ceritinib,genetic abnormalities

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Dose Limiting Toxicities (DLTs)

    The maximum tolerated dose (MTD) was defined as the highest dose for a given schedule that was expected to cause DLTs in no more than 33% of patients during the first cycle of treatment. A patient with multiple occurrences of a DLT under one treatment is counted only once in the AE category for that treatment. MTD was determined at 750mg.

    33 months

Secondary Outcomes (15)

  • Overall Response Rate (ORR) Based on Investigator Assessment

    275 weeks

  • Overall Response Rate Based on Blinded Independent Review Committee (BIRC) Assessment

    275 weeks

  • Duration of Response (DOR) Based on Investigator Assessment

    275 weeks

  • Duration of Response (DOR) Based on BIRC

    275 weeks

  • Progression-free Survival Based on Investigator Assessment

    275 weeks

  • +10 more secondary outcomes

Study Arms (3)

LDK378 750 mg: Arm 1A and Arm 1B

EXPERIMENTAL

NSCLC patients previously treated with an ALK inhibitor

Drug: LDK378

LDK378 750 mg: Arm 2

EXPERIMENTAL

NSCLC patients not previously treated with an ALK inhibitor

Drug: LDK378

LDK378 750 mg: Arm 3

EXPERIMENTAL

Patients with other tumors that are ALK positive other than NSCLC

Drug: LDK378

Interventions

LDK378DRUG

LDK378 is a selective and a potent inhibitor of anaplastic lymphoma kinase (ALK) activity, is a capsule and is administered orally.

LDK378 750 mg: Arm 1A and Arm 1BLDK378 750 mg: Arm 2LDK378 750 mg: Arm 3

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ECOG Performance Status of ≤ 2 and life expectancy of ≥ 12 weeks.
  • Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists. Only patients with tumors characterized by genetic abnormalities in ALK were enrolled.
  • For NSCLC, an ALK translocation must be detected by FISH in ≥ 15% of tumor cells.
  • In patients with diseases other than NSCLC, ALK translocation is not required and overexpression of ALK protein may be considered indicative of a genetic abnormality in ALK.
  • Patients with measurable or non-measurable disease as determined by modified RECIST version 1.0 in dose-escalation phase, and patients with at least one measurable lesion as determined by RECIST 1.0 in expansion phase.

You may not qualify if:

  • Patients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or required increasing doses of steroids to control their CNS disease were excluded.
  • Patients with a prior or current history of a second malignancy, impaired GI function, history of pancreatitis or increased amylase or lipase, known diagnosis of HIV, and clinically significant cardiac disease were excluded.
  • Patients treated with chemotherapy or biologic therapy or other investigational agent \< 2 weeks prior to starting study drug for compounds with a half-life ≤ 3 days, and \< 4 weeks prior to starting study drug for compounds with a prolonged half-life were excluded.
  • Further, patients treated with medications that were known to be strong inhibitors or inducers of CYP3A4/5 that could not be discontinued at least a week prior to start of treatment with LDK378 and for the duration of the study were also excluded.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

University of Colorado School of Medicine Colorado Univ

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital Mass General

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering MSK

New York, New York, 10017, United States

Location

Fox Chase Cancer Center Fox Chase Cancer (2)

Philadelphia, Pennsylvania, 19111, United States

Location

University of Utah / Huntsman Cancer Institute Huntsman

Salt Lake City, Utah, 84103, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98105, United States

Location

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1Z6, Canada

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Seoul, Korea, 03080, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Novartis Investigative Site

Leicester, LE1 5WW, United Kingdom

Location

Related Publications (4)

  • Tan DS, Thomas M, Kim DW, Szpakowski S, Urban P, Mehra R, Chow LQM, Sharma S, Solomon BJ, Felip E, Camidge DR, Vansteenkiste J, Petruzzelli L, Pantano S, Shaw AT. Genetic landscape of patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and response to ceritinib in ASCEND-1 study. Lung Cancer. 2022 Jan;163:7-13. doi: 10.1016/j.lungcan.2021.11.007. Epub 2021 Nov 20.

    PMID: 34890832DERIVED

  • Kim DW, Mehra R, Tan DSW, Felip E, Chow LQM, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Sutradhar S, Li S, Szczudlo T, Yovine A, Shaw AT. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol. 2016 Apr;17(4):452-463. doi: 10.1016/S1470-2045(15)00614-2. Epub 2016 Mar 11.

    PMID: 26973324DERIVED

  • Richly H, Kim TM, Schuler M, Kim DW, Harrison SJ, Shaw AT, Boral AL, Yovine A, Solomon B. Ceritinib in patients with advanced anaplastic lymphoma kinase-rearranged anaplastic large-cell lymphoma. Blood. 2015 Sep 3;126(10):1257-8. doi: 10.1182/blood-2014-12-617779. No abstract available.

    PMID: 26337354DERIVED

  • Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. doi: 10.1056/NEJMoa1311107.

    PMID: 24670165DERIVED

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ceritinib

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
862-778-8300

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 24, 2011

First Posted

January 26, 2011

Study Start

January 24, 2011

Primary Completion

May 3, 2016

Study Completion

May 3, 2016

Last Updated

March 15, 2019

Results First Posted

August 11, 2014

Record last verified: 2018-11

Locations

AU(1)DE(4)KR(1)NL(1)CA(1)GB(2)IT(2)BE(1)SG(1)ES(1)US(6)