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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 )

Tracking Information
First Submitted Date  ICMJE July 3, 2014
First Posted Date  ICMJE July 10, 2014
Results First Submitted Date  ICMJE December 11, 2018
Results First Posted Date  ICMJE April 8, 2021
Last Update Posted Date April 8, 2021
Actual Study Start Date  ICMJE September 17, 2014
Actual Primary Completion Date December 13, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2021)
  • 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)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 8, 2014)
Clinical benefit rate associated with ceritinib treatment [ Time Frame: 16 weeks ]
For patients with solid tumors the assessment criteria will be RECIST 1.1 and will include responses of CR or PR or SD ≥ 16 weeks. For hematologic tumors, other appropriate hematological response criteria will apply
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2021)
  • 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.
  • 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.
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2014)
  • Overall Response (OR) of Partial Response (PR) or greater [ Time Frame: Baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months ]
    For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors, other appropriate hematological response criteria will apply
  • Progression-Free Survival (PFS) [ Time Frame: every 8 weeks until death, assessed up to 24 months ]
    Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause
  • Overall Survival (OS) [ Time Frame: every 8 weeks until death, assessed up to 36 months ]
    Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause
  • Duration of Response (DOR) [ Time Frame: baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months ]
    Duration of response (DOR) is defined as time from the first documented response to the date first documented disease progression or relapse or death due to any cause
  • Safety and tolerability [ Time Frame: baseline up to 30 days after last study treatment ]
    Incidence of AEs, SAEs, changes from baseline in vital signs, laboratory test results (hematology, biochemistry), ECG, and cardiac imaging will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE), v4.03
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE)
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Tumors With Aberrations in ALK or ROS1
Intervention  ICMJE 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
Study Arms  ICMJE 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.
Intervention: Drug: Ceritinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 14, 2018)
47
Original Estimated Enrollment  ICMJE
 (submitted: July 8, 2014)
90
Actual Study Completion Date  ICMJE December 13, 2017
Actual Primary Completion Date December 13, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02186821
Other Study ID Numbers  ICMJE CLDK378AUS23
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP