A Dose Escalation/Expansion Study of LDK378 in Patients With Tumors Characterized by Genetic Abnormalities in Anaplastic Lymphoma Kinase

NCT ID: NCT01283516

Last Updated: 2019-03-15

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

304 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-01-24

Study Completion Date

2016-05-03

Brief Summary

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

Detailed Description

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Conditions

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Tumors Characterized by Genetic Abnormalities of ALK

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LDK378 750 mg: Arm 1A and Arm 1B

NSCLC patients previously treated with an ALK inhibitor

Group Type EXPERIMENTAL

LDK378

Intervention Type DRUG

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 2

NSCLC patients not previously treated with an ALK inhibitor

Group Type EXPERIMENTAL

LDK378

Intervention Type DRUG

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 3

Patients with other tumors that are ALK positive other than NSCLC

Group Type EXPERIMENTAL

LDK378

Intervention Type DRUG

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

Interventions

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LDK378

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of Colorado School of Medicine Colorado Univ

Aurora, Colorado, United States

Site Status

Massachusetts General Hospital Mass General

Boston, Massachusetts, United States

Site Status

Memorial Sloan Kettering MSK

New York, New York, United States

Site Status

Fox Chase Cancer Center Fox Chase Cancer (2)

Philadelphia, Pennsylvania, United States

Site Status

University of Utah / Huntsman Cancer Institute Huntsman

Salt Lake City, Utah, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Novartis Investigative Site

Melbourne, Victoria, Australia

Site Status

Novartis Investigative Site

Leuven, , Belgium

Site Status

Novartis Investigative Site

Toronto, Ontario, Canada

Site Status

Novartis Investigative Site

Cologne, North Rhine-Westphalia, Germany

Site Status

Novartis Investigative Site

Essen, , Germany

Site Status

Novartis Investigative Site

Heidelberg, , Germany

Site Status

Novartis Investigative Site

Ulm, , Germany

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Rozzano, MI, Italy

Site Status

Novartis Investigative Site

Amsterdam, , Netherlands

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Seoul, Korea, South Korea

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Glasgow, Scotland, United Kingdom

Site Status

Novartis Investigative Site

Leicester, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada Germany Italy Netherlands Singapore South Korea Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 34890832 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26973324 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26337354 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24670165 (View on PubMed)

Related Links

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Other Identifiers

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2010-019827-70

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLDK378X2101

Identifier Type: -

Identifier Source: org_study_id

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