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Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE) (SIGNATURE)

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ClinicalTrials.gov Identifier: NCT02186821
Recruitment Status : Terminated (Study was terminated due to low enrollment)
First Posted : July 10, 2014
Results First Posted : April 8, 2021
Last Update Posted : April 8, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this signal seeking study was to determine whether treatment with ceritinib demonstrated sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

Condition or disease Intervention/treatment Phase
Tumors With Aberrations in ALK or ROS1 Drug: Ceritinib Phase 2

Detailed Description:

This was an open label study to determine the efficacy and safety of treatment with ceritinib in patients with a diagnosis of solid tumors or hematological malignancies that had been pre-identified (prior to study consent) to have ALK or ROS1 positive mutations, translocations, rearrangements or amplifications and whose disease had progressed on or after standard treatment. The study consisted of a treatment phase where all patients received ceritinib capsules for a total dose of 750 mg daily for up to 8 cycles of 28 days. Disease assessments for clinical benefit were performed every 8 weeks until disease progression or end of treatment. Following discontinuation of treatment for any reason, patients were followed for safety for 30 days. Survival information was collected every 3 months until 2 years after the last patient had enrolled into the study. Study was amended to allow for discontinuation of survival period if primary endpoint was not met.

Study was terminated due to low enrollment.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module - 7 Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1
Actual Study Start Date : September 17, 2014
Actual Primary Completion Date : December 13, 2017
Actual Study Completion Date : December 13, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Ceritinib

Arm Intervention/treatment
Experimental: Ceritinib 750 mg
Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.
Drug: Ceritinib
Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally,once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days. There were no breaks between dosing cycles.
Other Name: LDK378




Primary Outcome Measures :
  1. Percentage of Participants Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) Utilizing RECIST 1.1 at Approximately 16 Weeks [ Time Frame: Baseline up to approximately 16 weeks ]
    Solid tumors were assessed using RECIST 1.1 criteria and included responses of complete response (CR) or partial response (PR) or stable disease (SD). For hematologic tumors, other hematological response criteria applied. CR=disappearance of all target lesions. Pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. PR=at least 30% decrease in sum of diameters of target lesions from baseline sum diameters. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive disease (PD)=at least a 20% increase in sum of diameter of measured target lesions from smallest sum of diameter of all target lesions recorded at or after baseline (sum must also demonstrate an absolute increase of at least 5mm). One or more new lesions was considered PD. Overall response rate (ORR) = (CR + PR). Clinical benefit rate = (CR + PR + SD)

  2. Number of Participants With Tumor Responses Utilizing RECIST 1.1 at Approximately 16 Weeks [ Time Frame: Baseline up to approximately 16 weeks ]
    For patients with solid tumors the assessment criteria was RECIST 1.1 and included responses of complete response (CR) or partial response (PR) or stable disease (SD). For hematologic tumors, other hematological response criteria applied. CR=disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. PR=at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive disease (PD)=at least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline (sum must also demonstrate an absolute increase of at least 5mm). One or more new lesions was also considered progression.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Baseline up to approximately 27 months ]
    Progression-free survival (PFS) was the time from the date of start of study drug to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a patient has not had an event, progression-free survival was censored at the date of last adequate tumor assessment.

  2. Percentage of Participants With Progression-Free Survival (PFS) - Kaplan-Meier Estimates [ Time Frame: Basleline up to approximately 27 months ]
    Progression-free survival (PFS) was the time from the date of start of study drug to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a patient has not had an event, progression-free survival was censored at the date of last adequate tumor assessment.

  3. Overall Survival (OS) - Number of Participant Deaths [ Time Frame: Baseline up to approximately 27 months ]
    Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause

  4. Duration of Response (DOR) [ Time Frame: baseline up to approximately 30 months ]
    Duration of response (DOR) is defined as time from the first documented response (CR or PR) to the date first documented disease progression or relapse or death due to any cause



Information from the National Library of Medicine

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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 had a confirmed diagnosis of a select solid tumor (except ALK+ NSCLC) or hematological malignancy and was in need of treatment because of radiologic progression or relapse.
  • Patient must have been pre-identified as having a tumor with an ALK or ROS1 positive mutation, translocation, rearrangement or amplification. The qualifying alteration must have been assessed and reported by a CLIA-certified laboratory. ALK positivity as assessed by IHC or FISH were allowed.
  • Patient must have received at least one prior treatment for recurrent, metastatic and/or locally advanced disease and for whom no standard therapy options were anticipated to result in a durable remission.
  • Patient had progressive and measurable disease as per RECIST 1.1 or other appropriate hematological guidelines.
  • Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

Exclusion Criteria:

  • Patient had received prior treatment with ceritinib.
  • Patients with symptomatic CNS metastases who were neurologically unstable or required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
  • Patient had received chemotherapy or anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, monoclonal antibodies or mitomycin-C) prior to starting study drug.

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): NCT02186821


Locations
Show Show 21 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] April 9, 2017
Study Protocol  [PDF] January 6, 2016

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02186821    
Other Study ID Numbers: CLDK378AUS23
First Posted: July 10, 2014    Key Record Dates
Results First Posted: April 8, 2021
Last Update Posted: April 8, 2021
Last Verified: March 2021
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
hematological malignancy
solid tumor malignancy
mutation
translocation
rearrangement
amplification
ALK
ROS1
NSCLC
B-cell lymphoma
Additional relevant MeSH terms:
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Neoplasms
Ceritinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action