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Ceritinib Rare Indications Study in ALK+ Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02465528
Recruitment Status : Terminated
First Posted : June 8, 2015
Results First Posted : October 21, 2019
Last Update Posted : December 27, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is Proof-of-Concept (POC) study to assess the preliminary antitumor activity and safety and tolerablity using ceritinib (LDK378) in the treatment of life threatening tumors that are characterized by ALK genetic alteration (and/or overexpression in some diseases).

Condition or disease Intervention/treatment Phase
Tumors With Aberrations in ALK Anaplastic Large Cell Lymphoma Inflammatory Myofibroblastic Tumor Glioblastoma Drug: Ceritinib (LDK378) Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Depending on the tumor type, subjects were to be enrolled into one of the following parallel arms: ALCL (anaplastic large cell lymphoma); IMT (inflammatory myofibroblastic tumor); glioblastoma (GBM), and any other ALK+ tumor. If there were 5 or more subjects of the same tumor type in the "Any other ALK+ tumor" arm, then a separate arm was to be opened for that specific tumor type.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open Label, Multi-center, Multi-arm Study of Ceritinib in Patients With Advanced Solid Tumors and Hematological Malignancies Characterized by Genetic Abnormalities of Anaplastic Lymphoma Kinase (ALK)
Actual Study Start Date : May 6, 2016
Actual Primary Completion Date : August 20, 2018
Actual Study Completion Date : August 20, 2018


Arm Intervention/treatment
Experimental: Inflammatory myofibroblastic tumor (IMT)
Patients diagnosed with IMT with a confirmed translocation involving the ALK gene
Drug: Ceritinib (LDK378)
Ceritinib was to be administered orally once daily at a dose of 750 mg (5 capsules of 150 mg) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib.

Experimental: Anaplastic large cell lymphoma (ALCL)
Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive
Drug: Ceritinib (LDK378)
Ceritinib was to be administered orally once daily at a dose of 750 mg (5 capsules of 150 mg) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib.

Experimental: Glioblastoma (GBM)
Patients with GBM with a translocation involving the ALK gene
Drug: Ceritinib (LDK378)
Ceritinib was to be administered orally once daily at a dose of 750 mg (5 capsules of 150 mg) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib.

Experimental: Any other ALK-positive tumor
Patients with any other ALK-positive tumor. Patients in this arm included adenocarcinoma (n= 2), sarcoma (1) and other (2).
Drug: Ceritinib (LDK378)
Ceritinib was to be administered orally once daily at a dose of 750 mg (5 capsules of 150 mg) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib.




Primary Outcome Measures :
  1. Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment [ Time Frame: Baseline up to approximately 16 weeks ]
    The DCR is defined as the percentage of patients with complete response (CR), partial response (PR) or stable disease (SD) at 16 weeks from the start of ceritinib treatment. The assessment criteria are: Solid Tumors (RECIST 1.1., Response Evaluation Criteria in Solid Tumors); GBM (RECIST 1.1 and RANO, Response Evaluation in Neuro-Oncology); Hematologic tumors (Cheson).


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) Per Investigator Assessment [ Time Frame: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first assessed up to approximately 84 weeks ]
    ORR is defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local assessment according to RECIST 1.1, RANO or Cheson hematological criteria.

  2. Duration of Response (DOR) Per Investigator Assessment [ Time Frame: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks ]
    DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause

  3. Time to Response (TTR) Per Investigator Assessment [ Time Frame: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks ]
    TTR is defined as the time from date of the first dose to date of first documented response (CR or PR)

  4. Progression Free Survival (PFS) Per Investigator Assessments [ Time Frame: Baseline, every 8 weeks until disease progression or death from any cause, assessed for up to approximately 84 weeks ]
    PFS is defined as the time from the date of first dose of ceritinib to the date of first documented disease progression or death from any cause

  5. Percent of Participant Deaths During Treatment and Follow-up [ Time Frame: Baseline up to approximately 84 weeks ]
    Deaths due to any cause during treatment and 30 day follow-up



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has a histologically or cytologically confirmed diagnosis of ALK positive (ALK+) tumor other than Non-Small Cell Lung Cancer (NSCLC).
  • Patient must provide an archival or fresh tumor tissue before the first dose of the study drug for ALK testing at a Novartis designated central laboratory.
  • Patient has WHO Performance Status (PS) ≤ 2
  • Patient must have received at least one line of prior systemic treatment for recurrent, locally advanced and/or metastatic disease, and may have discontinued for:

    • Disease progression as defined by RECIST 1.1 for solid tumors; by RANO for GBM and by Cheson assessment criteria for lymphoma, or
    • Intolerance described as any discontinuation due to an AE of any grade despite appropriate supportive treatment
  • Patient has at least one measurable lesion as defined by appropriate guidelines. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation.
  • Patient has received no chemotherapy, immunotherapy or stem cell therapy at least 4 weeks before starting ceritinib
  • Radiotherapy and prior ALK inhibitors must be stopped at least 1 week prior to starting ceritinib
  • Recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (Common Terminology Criteria for Adverse Events [CTCAE] v4.03).

Exclusion Criteria:

  • Patient has ALK+lung cancer
  • Patient with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
  • Patient with acute or chronic GI disease that may significantly alter the absorption of ceritinib.
  • Patient with a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
  • Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
  • Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months).
  • Patient has evidence of active viral hepatitis, including Hepatitis A, B or C (testing for viral hepatitis is not mandatory).
  • Patient has known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02465528


Locations
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Czechia
Novartis Investigative Site
Brno, Czech Republic, Czechia, 656 53
Denmark
Novartis Investigative Site
Copenhagen, Denmark, DK-2100
France
Novartis Investigative Site
Lyon Cedex, France, 69373
Novartis Investigative Site
Saint-Herblain Cédex, France, 44805
Novartis Investigative Site
Strasbourg, France, F 67085
Israel
Novartis Investigative Site
Tel Aviv, Israel, 6423906
Italy
Novartis Investigative Site
Milano, MI, Italy, 20133
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Republic of, 03080
Novartis Investigative Site
Seoul, Korea, Republic of, 03722
Novartis Investigative Site
Seoul, Korea, Republic of, 06351
Spain
Novartis Investigative Site
Madrid, Spain, 28034
Novartis Investigative Site
Madrid, Spain, 28040
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10330
Novartis Investigative Site
Bangkok, Thailand, 10700
Sponsors and Collaborators
Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] November 30, 2015
Statistical Analysis Plan  [PDF] September 20, 2018

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02465528    
Other Study ID Numbers: CLDK378A2407
First Posted: June 8, 2015    Key Record Dates
Results First Posted: October 21, 2019
Last Update Posted: December 27, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
ALK
GBM
hematological malignancy
anaplastic lymphoma kinase
glioblastoma
anaplastic large cell lymphoma
IMT
inflammatory myofibroblastic tumor
Additional relevant MeSH terms:
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Lymphoma
Glioblastoma
Lymphoma, Large-Cell, Anaplastic
Granuloma, Plasma Cell
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Lymphoma, T-Cell
Lymphoma, Non-Hodgkin
Granuloma
Pathologic Processes
Ceritinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action