Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE)
- Registration Number
- NCT02186821
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 47
- 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 โค 1.
- 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 โค 4 weeks (6 weeks for nitrosourea, monoclonal antibodies or mitomycin-C) prior to starting study drug.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ceritinib 750 mg 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 with no breaks between dosing cycles.
- Primary Outcome Measures
Name Time Method Percentage of Participants Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) Utilizing RECIST 1.1 at Approximately 16 Weeks 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 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
Name Time Method Progression-Free Survival (PFS) 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 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 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) 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
Trial Locations
- Locations (21)
Columbus Hematology and Oncology PA Columbus Hem and Onc (2)
๐บ๐ธColumbus, Ohio, United States
MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
๐บ๐ธHouston, Texas, United States
Swedish Cancer Institute Swedish Cancer Institute
๐บ๐ธSeattle, Washington, United States
Duke University Medical Center Seeley G. Mudd Bldg.
๐บ๐ธDurham, North Carolina, United States
Sanford Hematology Oncology
๐บ๐ธFargo, North Dakota, United States
Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
๐บ๐ธLas Vegas, Nevada, United States
Holy Cross Hospital Holy Cross (2)
๐บ๐ธSilver Spring, Maryland, United States
Utah Cancer Specialists Utah Cancer Specialists
๐บ๐ธSalt Lake City, Utah, United States
Aurora Research Institute
๐บ๐ธMilwaukee, Wisconsin, United States
Florida Cancer Specialists Florida Cancer Specialists (31
๐บ๐ธFort Myers, Florida, United States
Southeast Nebraska Oncology
๐บ๐ธLincoln, Nebraska, United States
Sanford University of South Dakota Medical Center Sanford Clinical Research
๐บ๐ธSioux Falls, South Dakota, United States
Northwestern University Northwestern (6)
๐บ๐ธChicago, Illinois, United States
Oncology Consultants Oncology Group
๐บ๐ธHouston, Texas, United States
Sarah Cannon Research Institute
๐บ๐ธDenver, Colorado, United States
Rocky Mountain Cancer Centers Dept of Rocky Mountain (2)
๐บ๐ธGreenwood Village, Colorado, United States
St Joseph Heritage Healthcare St. Joseph Heritage
๐บ๐ธSanta Rosa, California, United States
Physicians Clinic of Iowa
๐บ๐ธCedar Rapids, Iowa, United States
Wake Forest Baptist Health Health Sciences
๐บ๐ธWinston-Salem, North Carolina, United States
Andrew and Patel Associates
๐บ๐ธCamp Hill, Pennsylvania, United States
Rhode Island Hospital Rhode Island Hosp. (2)
๐บ๐ธProvidence, Rhode Island, United States
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