Study Stopped
Study was terminated due to low enrollment
Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE)
SIGNATURE
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
1 other identifier
interventional
47
1 country
21
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Sep 2014
Typical duration for phase_2
21 active sites
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
July 3, 2014
CompletedFirst Posted
Study publicly available on registry
July 10, 2014
CompletedStudy Start
First participant enrolled
September 17, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 13, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
December 13, 2017
CompletedResults Posted
Study results publicly available
April 8, 2021
CompletedApril 8, 2021
March 1, 2021
3.2 years
July 3, 2014
December 11, 2018
March 12, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) Utilizing RECIST 1.1 at 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)
Baseline up to approximately 16 weeks
Number of Participants With Tumor Responses Utilizing RECIST 1.1 at 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.
Baseline up to approximately 16 weeks
Secondary Outcomes (4)
Progression-Free Survival (PFS)
Baseline up to approximately 27 months
Percentage of Participants With Progression-Free Survival (PFS) - Kaplan-Meier Estimates
Basleline up to approximately 27 months
Overall Survival (OS) - Number of Participant Deaths
Baseline up to approximately 27 months
Duration of Response (DOR)
baseline up to approximately 30 months
Study Arms (1)
Ceritinib 750 mg
EXPERIMENTALCeritinib 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
St Joseph Heritage Healthcare St. Joseph Heritage
Santa Rosa, California, 94503, United States
Sarah Cannon Research Institute
Denver, Colorado, 80218, United States
Rocky Mountain Cancer Centers Dept of Rocky Mountain (2)
Greenwood Village, Colorado, United States
Florida Cancer Specialists Florida Cancer Specialists (31
Fort Myers, Florida, 33901, United States
Northwestern University Northwestern (6)
Chicago, Illinois, 60611, United States
Physicians Clinic of Iowa
Cedar Rapids, Iowa, 52403, United States
Holy Cross Hospital Holy Cross (2)
Silver Spring, Maryland, 20910, United States
Southeast Nebraska Oncology
Lincoln, Nebraska, 68510, United States
Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
Las Vegas, Nevada, 89109, United States
Duke University Medical Center Seeley G. Mudd Bldg.
Durham, North Carolina, 27710, United States
Wake Forest Baptist Health Health Sciences
Winston-Salem, North Carolina, 27157, United States
Sanford Hematology Oncology
Fargo, North Dakota, 58122, United States
Columbus Hematology and Oncology PA Columbus Hem and Onc (2)
Columbus, Ohio, 39705, United States
Andrew and Patel Associates
Camp Hill, Pennsylvania, 17011, United States
Rhode Island Hospital Rhode Island Hosp. (2)
Providence, Rhode Island, 02903, United States
Sanford University of South Dakota Medical Center Sanford Clinical Research
Sioux Falls, South Dakota, 57104, United States
Oncology Consultants Oncology Group
Houston, Texas, 77024, United States
MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
Houston, Texas, 77030, United States
Utah Cancer Specialists Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
Swedish Cancer Institute Swedish Cancer Institute
Seattle, Washington, 98104, United States
Aurora Research Institute
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 3, 2014
First Posted
July 10, 2014
Study Start
September 17, 2014
Primary Completion
December 13, 2017
Study Completion
December 13, 2017
Last Updated
April 8, 2021
Results First Posted
April 8, 2021
Record last verified: 2021-03